Ubiquitous coexisting electron-mode couplings in high-temperature cuprate superconductors.

In conventional superconductors, electron-phonon coupling plays a dominant role in generating superconductivity. In high-temperature cuprate superconductors, the existence of electron coupling with phonons and other boson modes and its role in producing high-temperature superconductivity remain unclear. The evidence of electron-boson coupling mainly comes from angle-resolved photoemission (ARPES) observations of [Formula: see text]70-meV nodal dispersion kink and [Formula: see text]40-meV antinodal kink. However, the reported results are sporadic and the nature of the involved bosons is still under debate. Here we report findings of ubiquitous two coexisting electron-mode couplings in cuprate superconductors. By taking ultrahigh-resolution laser-based ARPES measurements, we found that the electrons are coupled simultaneously with two sharp modes at [Formula: see text]70meV and [Formula: see text]40meV in different superconductors with different dopings, over the entire momentum space and at different temperatures above and below the superconducting transition temperature. These observations favor phonons as the origin of the modes coupled with electrons and the observed electron-mode couplings are unusual because the associated energy scales do not exhibit an obvious energy shift across the superconducting transition. We further find that the well-known "peak-dip-hump" structure, which has long been considered a hallmark of superconductivity, is also omnipresent and consists of "peak-double dip-double hump" finer structures that originate from electron coupling with two sharp modes. These results provide a unified picture for the [Formula: see text]70-meV and [Formula: see text]40-meV energy scales and their evolutions with momentum, doping and temperature. They provide key information to understand the origin of these energy scales and their role in generating anomalous normal state and high-temperature superconductivity.

A randomized, double-blind, placebo-controlled trial to evaluate the role of curcumin in prostate cancer patients with intermittent androgen deprivation.

BACKGROUND: The anti-cancer activities of curcumin are well-documented from preclinical studies using prostate cancer models. Our objective was to evaluate the anti-cancer activity of oral curcumin in patients with prostate cancer. METHODS: This randomized, double-blind, placebo-controlled trial was performed on patients with prostate cancer who received intermittent androgen deprivation (IAD). Participants who finished the first on-treatment period of IAD were randomized into a curcumin or placebo group. The patients took oral curcumin (1440 mg/day) or placebo for six months and were followed up until the beginning of the second on-treatment. The primary end-point was duration of the first off-treatment. The secondary end-points were change in PSA and testosterone levels during 6 months, PSA progression rate, and health-related quality of life (HRQOL) scores at 6 months. Safety assessments included adverse event, adverse drug reaction, and serious adverse event. RESULTS: A total of 97 participants were randomized 1:1 to curcumin (n = 49) and placebo (n = 48) groups. Among them, 82 patients (84.5%) were evaluable for the analysis (39 and 43 patients in the curcumin and placebo groups, respectively). The median off-treatment duration was 16.3 months (95% confidence interval [CI] 12.3-20.3 months) and 18.5 months (95% CI 12.5-23.0 months) in the curcumin and placebo groups, respectively. There was no significant difference in the curve of off-treatment duration between the two groups (P = 0.4816). The proportion of patients with PSA progression during the active curcumin treatment period (6 months) was significantly lower in the curcumin group than the placebo group (10.3% vs 30.2%, P = 0.0259). The change of PSA, testosterone levels during 6 months, and HRQOL scores at 6 months were not different between curcumin and placebo groups. Adverse events were higher in the placebo group (16 of 46 vs 7 of 45 patients, P = 0.0349). No significant differences in the adverse drug reaction were found between the two groups. CONCLUSIONS: Six months' intake of oral curcumin did not significantly affect the overall off-treatment duration of IAD. However, PSA elevation was suppressed with curcumin intake during the curcumin administration period. Curcumin at this dose was well tolerated and safe.

A retrospective feasibility study of biweekly docetaxel in patients with high-risk metastatic castration-naïve prostate cancer.

BACKGROUND: Results from randomized phase III trials have shown that thrice-weekly docetaxel added to androgen-deprivation therapy (ADT) has a significant impact on the survival of patients with metastatic castration-naïve prostate cancer (mCNPC) and established early chemotherapy as part of the standard of care for high-risk disease. Controversy remains, however, because some patients experience critical toxicities related to docetaxel. The purpose of the current study was to evaluate the feasibility and adverse events of biweekly-administered docetaxel in patients with previously-untreated, high-risk mCNPC. METHODS: The study included 35 consecutive patients with high-risk mCNPC who received ADT plus docetaxel 40 mg/m2. Oral prednisone 5 mg twice daily was also given. Treatment was repeated every two weeks for up to 12 cycles or until disease progression or unacceptable toxicity occurred. High-risk was defined as bone metastases beyond axial skeleton and/or visceral disease. RESULTS: The included patients' median age was 68 years (range: 31-86 years) and 17 (49%) had visceral metastases. Biweekly docetaxel was generally well-tolerated; the most commonly observed adverse events, considering those of all grades, included alopecia (74%), nail changes (42%), and constipation (31%). Hematologic adverse events were infrequent, and no patient received hematopoietic growth factors. One patient died after the fourth cycle due to respiratory failure, which occurred as a complication of pneumonia. Among the 35 patients, 28 completed the planned 12 cycles of biweekly docetaxel. Prostate-specific antigen response (> 50% decrease from baseline) was recorded in 33 patients (94%), and the radiologic response rate was 49%. Median progression-free survival was 13.6 months (95% confidence interval: 6.7-20.4). CONCLUSION: ADT plus biweekly-administered docetaxel appeared to be tolerated and effective in patients with high-risk mCNPC.

Changeable Conditional Survival Rates and Associated Prognosticators in Patients with Metastatic Renal Cell Carcinoma Receiving First Line Targeted Therapy.

PURPOSE: In this study we evaluated conditional survival probabilities in patients with metastatic renal cell carcinoma who underwent first line tyrosine kinase inhibitor therapy. We also identified predictors of conditional survival with time. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 1,659 individuals with metastatic renal cell carcinoma in the Korean Renal Cancer Study Group database, of whom the records of 1,131 were finally analyzed. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities using the formula, conditional survival (α│ß) = S(α + ß)/S(ß), indicating the likelihood of additional α years survivorship in person who has already survived for ß years after initial therapy. S(χ) represents the actual survival rate. Multivariate Cox regression model was used to identify predictors of conditional survival with time. RESULTS: Six, 12, 18, 24 and 36-month conditional overall survival gradually increased in patients at all additional survival times after initial treatment compared to patient baseline survival estimations. While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment. Furthermore, predictors of conditional overall survival changed with time. Only previous metastasectomy remained a key prognosticator of conditional overall survival until 36 months of survival following initial tyrosine kinase inhibitor treatment. CONCLUSIONS: Conditional survival improved with time after initial tyrosine kinase inhibitor treatment in patients with metastatic renal cell carcinoma. Our study offers valuable information for practical survival estimations and relevant prognosticators in patients with metastatic renal cell carcinoma who receive first line tyrosine kinase inhibitor.

Prognostic impact of the pretreatment aspartate transaminase/alanine transaminase ratio in patients treated with first-line systemic tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma.

OBJECTIVES: To examine the prognostic role of the pretreatment aspartate transaminase/alanine transaminase or De Ritis ratio in patients with metastatic renal cell carcinoma receiving first-line systemic tyrosine kinase inhibitor therapy. METHODS: We retrospectively searched the medical records of 579 patients with metastatic renal cell carcinoma who visited Samsung Medical Center, Seoul, Korea, from January 2001 through August 2016. After excluding 210 patients, we analyzed 360 patients who received first-line tyrosine kinase inhibitor therapy. Cancer-specific survival and overall survival were defined as the primary and secondary end-points, respectively. A multivariate Cox proportional hazards regression model was used to identify independent prognosticators of survival outcomes. RESULTS: The overall population was divided into two groups according to the pretreatment De Ritis ratio as an optimal cut-off value of 1.2, which was determined by a time-dependent receiver operating characteristic curve analysis. Patients with a higher pretreatment De Ritis ratio (≥1.2) had worse cancer-specific survival and overall survival outcomes, compared with those with a lower De Ritis ratio (<1.2). Notably, a higher De Ritis ratio (≥1.2) was found to be an independent predictor of both cancer-specific survival (hazard ratio 1.61, 95% confidence interval 1.13-2.30) and overall survival outcomes (hazard ratio 1.69, 95% confidence interval 1.19-2.39), along with male sex, multiple metastasis (≥2), non-clear cell histology, advanced pT stage (≥3), previous metastasectomy and the Memorial Sloan Kettering Cancer Center risk classification. CONCLUSION: Our findings show that the pretreatment De Ritis ratio can provide valuable information about the survival outcomes of metastatic renal cell carcinoma patients receiving first-line tyrosine kinase inhibitor therapy.

Postoperative Outcome of Cystic Renal Cell Carcinoma Defined on Preoperative Imaging: A Retrospective Study.

PURPOSE: We evaluated the postoperative outcome of cystic renal cell carcinoma defined on preoperative computerized tomography. We also sought to find the optimal cutoff of the cystic proportion in association with patient prognosis. MATERIAL AND METHODS: In this institutional review board approved study with waiver of informed consent, 1,315 patients were enrolled who underwent surgery for a single renal cell carcinoma with preoperative computerized tomography. The cystic proportion of renal cell carcinoma was determined on computerized tomography. The optimal cutoff of the cystic proportion was explored regarding cancer specific survival. Renal cell carcinomas were categorized as cystic or noncystic renal cell carcinoma according to a conventional cutoff (ie cystic proportion 75% or greater) and an optimal cutoff. Postoperative outcomes were then compared between the 2 groups. Multivariate Cox regression analysis was performed to determine the independent predictor of cancer specific survival. RESULTS: Of the 1,315 lesions 107 (8.1%) were identified as cystic renal cell carcinoma according to a conventional cutoff. The postoperative outcome of cystic renal cell carcinoma was significantly better than that of noncystic renal cell carcinoma (p <0.001). Neither metastasis nor recurrence developed after surgery in patients with cystic renal cell carcinoma. In association with the cancer specific survival rate, the optimal cutoff of the cystic proportion was 45% and 197 cases (15.0%) were accordingly defined as cystic renal cell carcinoma. On Cox regression analysis, a cystic proportion of 45% or greater of the renal cell carcinoma was an independent predictor of a favorable outcome regarding cancer specific survival (HR 0.34, p = 0.03). CONCLUSIONS: Cystic renal cell carcinoma defined on preoperative computerized tomography is associated with low metastatic potential and favorable outcomes after surgery. Particularly, a cystic proportion of 45% or greater is an independent prognostic factor for favorable survival.

Prognostic Significance of Pre- to Postoperative Dynamics of the Prognostic Nutritional Index for Patients with Renal Cell Carcinoma Who Underwent Radical Nephrectomy.

BACKGROUND: This study aimed to examine the prognostic role of Prognostic Nutritional Index (PNI) dynamics in the pre- and postoperative periods for patients with renal cell carcinoma (RCC) who undergo radical nephrectomy (RN). METHODS: The study analyzed 324 patients with RCC who underwent RN. The overall population was classified into four groups according to four types of pre- to postoperative PNI dynamics as follows: group 1 (low â†’ low PNI), group 2 (low â†’ high PNI), group 3 (high â†’ low PNI), and group 4 (high â†’ high PNI). The level of PNI was calculated using the following formula: 10 × serum albumin level (g/dL) + 0.005 × absolute lymphocyte counts in blood (/mm3). The primary end point was cancer-specific survival (CSS), and the secondary end point was overall survival (OS). RESULTS: The patients with higher pre- and postoperative PNI (>45) had better survival outcomes than those with lower pre- and postoperative PNI (≤45). Notably, the patients in group 4 showed the best CSS and OS rates, whereas the patients in group 1 had the worst survival outcomes. Furthermore, PNI dynamics were identified as an independent predictor of CSS and OS outcomes, in addition to pre- and postoperative PNI, tumor size, and pathologic T (pT) stage. The patients with localized RCC (≤pT2) showed significant differences in both CSS and OS estimates, whereas the patients with advanced pT stage (≥pT3) demonstrated a difference only in OS outcomes, according to PNI dynamics. CONCLUSIONS: This study is the first to provide the independent prognostic importance of dynamics of nutritional status for patients with RCC.

Accuracy of preoperative multiparametric magnetic resonance imaging for prediction of unfavorable pathology in patients with localized prostate cancer undergoing radical prostatectomy.

INTRODUCTION: We investigated the accuracy of multiparametric MRI (mpMRI) for preoperative staging and its influence on the determination of neurovascular bundle sparing and disease prognosis in patients with localized prostate cancer. METHODS: We reviewed 1045 patients who underwent radical prostatectomy with preoperative mpMRI at a single institution. Clinical local stages determined from mpMRI were correlated with preoperative and postoperative pathological outcomes. RESULTS: The sensitivity and specificity to diagnose seminal vesicle invasion (SVI) on mpMRI were 43.8 and 95.4 %, respectively. The negative predictive value was 78.9 %. The sensitivity and specificity to diagnose extracapsular extension (ECE) were 54.5 and 80.5 %, respectively. The overall sensitivity and specificity of diagnosing pathological T3 or higher were 52.6 and 82.1 %, respectively. Non-organ-confined disease determined by mpMRI was significantly associated with positive surgical margin and pathological T3 disease on multivariate analysis. Preoperative adverse findings on mpMRI were significantly associated with performance of the non-nerve-sparing technique. CONCLUSION: mpMRI did not show outstanding diagnostic accuracy relative to our expectations in predicting SVI or ECE preoperatively. However, adverse findings on preoperative mpMRI were significantly related to worse postoperative pathological outcomes as well as postoperative biochemical recurrence.

A retrospective feasibility study of biweekly, reduced-dose docetaxel in Asian patients with castrate-resistant, metastatic prostate cancer.

BACKGROUND: The aim of this retrospective study was to evaluate the clinical outcomes of reduced dose, biweekly docetaxel chemotherapy for Korean patients with castrate-resistant prostate cancer (CRPC). METHODS: We retrospectively reviewed the medical records of 48 patients with metastatic CRPC who were treated with a biweekly regimen (intravenous docetaxel 40 mg/m2 on day 1 plus prednisolone 5 mg twice daily) between 2012 and 2015 at Samsung Medical Center (Seoul, Korea). Prior to the adoption of a biweekly regimen in Oct 2013, our institutional standard chemotherapy was docetaxel 75 mg/m2 every 3 weeks for patients with CRPC (n = 24). After Oct 2013, all chemotherapy-naïve patients with CRPC received a 40 mg/m2 biweekly regimen (n = 24). The primary end point was a PSA response, defined as a greater than 50% decline in PSA level from baseline. RESULTS: The baseline characteristics of the patients in the two treatment groups were similar. The most common cause of treatment discontinuation was disease progression, which was exhibited by 17 patients (71%) in the 3-weekly group and 20 (75%) in the biweekly group. PSA responses were observed in 12 (50%) and 11 (46%) patients in the 3-weekly and biweekly groups, respectively (p = 0.683). Time to treatment failure (TTTF, 4.5 vs 3.9 months) and time-to-progression (TTP, 5.0 vs 4.2 months) were not significantly different between the 3-weekly and biweekly groups. CONCLUSIONS: Within the limitations of a retrospective study, the biweekly reduced dose docetaxel regimen was active and well-tolerated in Korean patients with metastatic CRPC.

Percutaneous Kidney Biopsy for a Small Renal Mass: A Critical Appraisal of Results.

PURPOSE: We report the diagnostic accuracy of renal mass biopsy for a small renal mass (4 cm or less) and identify predictors of successful renal mass biopsy in a contemporary cohort of patients from 2 large tertiary referral centers. MATERIALS AND METHODS: A total of 442 biopsies of renal tumors 4 cm or less at 2 tertiary centers between 2008 and 2015 were included in study. Biopsy outcomes (malignant, benign or nondiagnostic) and concordance rates between renal mass biopsy and final surgical pathology were determined. Univariate and multivariate logistic regression analyses were performed to identify factors indicative of nondiagnostic biopsy. RESULTS: The initial biopsy was diagnostic in 393 cases (88.9%) and nondiagnostic in 49 (11.1%). Of diagnostic biopsies 76% revealed renal cell carcinoma and 24% were benign. Renal cell carcinoma histological subtyping and grading was possible in 90.2% and 31.3% of cases, respectively. A second biopsy was performed in 11 of the 49 nondiagnostic cases and a diagnosis was possible in 100%, including renal cell carcinoma in 10 and oncocytoma in 1. Small tumor size, cystic nature of tumors and biopsy during the initial years of the study were independent predictors of nondiagnostic biopsy. The rates of accuracy in identifying malignancies, histiotyping and 2-tier grading between renal mass biopsy and surgical pathology were 97.1%, 95.1% and 68.8%, respectively. CONCLUSIONS: Renal mass biopsy for a small renal mass can be performed accurately. Nondiagnostic renal mass biopsy was common for smaller masses and cystic masses, and during the initial years of the study. A second biopsy should be considered in nondiagnostic biopsy cases.

Preoperative Prognostic Nutritional Index is a Significant Predictor of Survival in Renal Cell Carcinoma Patients Undergoing Nephrectomy.

BACKGROUND: Preoperative assessment of patients' immunologic and nutritional conditions is required to predict the outcome of patients with malignant tumors. The aim of the current study was to clarify the significance of the prognostic nutritional index (PNI), which simply accounts for immunological and nutritional conditions, in patients with renal cell carcinoma (RCC). METHODS: We included 1437 patients who underwent nephrectomy for RCC between 1994 and 2008. PNI was calculated using the following formula: 10 × serum albumin concentration (g/dL) + 0.005 × lymphocyte counts (number/mm(2)) in peripheral blood. We examined the correlation of the preoperative PNI value with clinicopathological features. A Cox regression model and the Harrell concordance index with variables only or combined PNI data were used to evaluate the prognostic significance in the T1-4NallMall and T1-4N0M0 groups. RESULTS: The mean preoperative PNI value was 52.7 ± 6.3 (range 27.7-85.3). The mean PNI values were significantly lower in patients with more advanced tumor T stage, regional lymph node metastasis, distant metastases, higher Fuhrman grade, and sarcomatoid differentiation than in patients without such factors (p < 0.001). Patients with low PNI (<51) had poor survival rates compared to those with high PNI in univariate analysis (>51, p < 0.001). Multivariate analysis showed that low PNI was significantly associated with cancer-specific survival (p = 0.026 and p = 0.009) and overall survival (p = 0.013 and p = 0.011) in the T1-4NallMall and T1-4N0M0 groups, respectively, after correcting for other clinicopathological factors. CONCLUSIONS: PNI is an independent prognostic factor for predicting survival after nephrectomy in patients with RCC.

Volumetric measurement of compensatory hypertrophy in the contralateral normal kidney by the tumor growth.

PURPOSE: We evaluated the association between tumor size and preoperative volumetric kidney parameters measured with CT in patients with renal cell carcinoma (RCC). METHODS: We prospectively identified 1118 patients who underwent radical or partial nephrectomy for RCC between 2011 and 2014. Contrast-enhanced CT was performed within three months before surgery. Kidney volume was measured using a tissue segmentation tool program from CT images. We classified patients into three groups depending on tumor size (A: ≤4 cm, B: 4-7 cm, C: >7 cm). The preoperative volumetric kidney parameters were compared and multivariable linear regression was used to analyze potential factors associated with compensatory hypertrophy of the contralateral normal kidney before surgery. RESULTS: Patients in group C had a significantly larger contralateral normal kidney volume than patients in A and B (A: 170.0 mL, B: 171.7 mL, C: 187.2 mL, p < 0.001). The contralateral kidney volume was not significantly different between groups A and B (p > 0.05). However, tumor-side real kidney volume in group C was significantly smaller than that of groups A and B (A: 168.8 mL, B: 164.9 mL, C: 150.9 mL, p < 0.001). On multivariable analysis, increased contralateral kidney volume was positively associated with male gender, higher BMI, DM, higher preoperative GFR, and tumor size (>7 cm), and negatively associated with older age (p < 0.05). Tumor size had the strongest positive association with contralateral kidney volume (>7 cm, partial regression coefficient = 30.2). CONCLUSIONS: Tumor size (>7 cm) is the strongest factor associated with compensatory hypertrophy in the contralateral normal kidney before surgery.

The impact of three-dimensional tumor volume on cancer-specific survival for patients with pT1 clear-cell renal cell carcinoma.

PURPOSE: To evaluate the impact of three-dimensional tumor volume on cancer-specific survival for patients with pT1 clear-cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We reviewed a prospectively maintained database of 917 patients who underwent radical nephrectomy or nephron-sparing surgery for unilateral, pT1 ccRCC, including 654 pT1a and 263 pT1b patients, between April 1997 and December 2010. Three-dimensional tumor volume was measured using specialized volumetric software on cross-sectional computed tomography images of a preoperative venous phase. Kaplan-Meier and Cox regression analyses were carried out. RESULTS: The median age was 54 years with a follow-up of 60.8 months. Median tumor size and volume were 3.2 cm and 17.4 cm(3), respectively. Of 917 patients, 54 (5.9 %) had died, including 32 patients with ccRCC (9 patients in pT1a and 23 patients in pT1b). On multivariate analysis, tumor size >3.2 cm and tumor volume >17.4 cm(3) were associated with cancer-specific death in pT1 ccRCC patients. When stratified by pT1a/pT1b status and analyzed on median splits, tumor size >2.5 cm was associated with cancer-specific death but not tumor volume >9.5 cm(3) in pT1a patients. However, in pT1b patients, tumor volume >62.1 cm(3) (P = 0.036, HR 2.91, 95 % CI 1.02-7.77) was highly associated with cancer-specific death but not tumor size >5.0 cm (P = 0.159, HR 1.91, 95 % CI 0.78-4.70). CONCLUSIONS: In addition to tumor size, tumor volume is associated with cancer-specific death in pT1 ccRCC patients, particularly in pT1b ccRCC but not in pT1a ccRCC.

A Prospective Multicenter Trial of the Efficacy and Tolerability of Neoadjuvant Sunitinib for Inoperable Metastatic Renal Cell Carcinoma.

This study aimed to evaluate the efficacy, safety, and tolerability of 2-cycled neoadjuvant sunitinib therapy (NST) in patients with inoperable metastatic renal cell carcinoma (mRCC). Between 2009 and 2012, 14 patients with inoperable mRCC from 5 Korean academic centers were prospectively enrolled after collecting their clinicopathological data and completing health-related questionnaires. The best overall response (BOR), safety profile, and changes in quality of life during NST were assessed using the RECIST criteria (version 1.0), CTCAE criteria (version 4.0), and the Cancer Quality of Life Questionnaire (QLQ-C30). Among the 14 patients, 9 patients (64.3%) experienced partial response or stable disease state, and 5 patients (35.7%) did not complete treatment, with 1 case of disease progression (7.1%), 3 grade 3 adverse events (21.4%), and 1 voluntary withdrawal (7.1%). Four patients (28.6%) were successfully converted to an operable state and underwent surgery after NST. The BOR for the primary renal lesions was 22.2%, with a median 1.3-cm diameter reduction (range: 0-2.8 cm) from a baseline diameter of 10.3 cm (range: 6.6-15.8 cm). The other 18 measurable metastatic lesions exhibited a BOR of 55.6%. The QLQ-C30 questionnaire results revealed significant improvements in the quality of life domain, although we observed significant increases in the scores for fatigue, nausea and vomiting, and the financial effects of NST (P < 0.05). Two-cycle NST provided limited efficacy for resectability of inoperable mRCC, despite mild improvements in the BOR of the primary lesion and quality of life (Clinical Trial Registry 1041140-1).

Comparison of preoperative adaptive enlargement of the contralateral normal kidney in patients nephrectomized for benign non-functioning kidney versus renal cell carcinoma.

OBJECTIVES: To investigate the potential effects of preoperative volumetric compensation of the contralateral normal kidney on renal function after simple nephrectomy or radical nephrectomy. METHODS: A total of 306 patients (80 simple nephrectomy patients and 226 radical nephrectomy patients) with 1:3 propensity score matching were included between October 1996 and December 2013. Preoperative three-dimensional kidney volume was estimated from computed tomography images using a specialized volumetric program. Glomerular filtration rate assessed using the Chronic Kidney Disease Epidemiology Collaboration equations was checked preoperatively, 1 week, 3 months and 1 year after nephrectomy. RESULTS: Preoperative mean Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate was 76.5 mL/min/1.73 m(2) in the simple nephrectomy group and 89.2 mL/min/1.73 m(2) in the radical nephrectomy group. In simple nephrectomy patients, mean Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate showed a stable pattern up to 3 months (75.5 mL/min/1.73 m(2) at 7 days and 76.2 mL/min/1.73 m(2) at 3 months), and decreased slightly to 72.6 mL/min/1.73 m(2) at 1 year. However, in radical nephrectomy patients, mean Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate decreased immediately to 63.4 mL/min/1.73 m(2) at 7 days after surgery, and then increased gradually to 64.6 mL/min/1.73 m(2) at 3 months and 65.9 mL/min/1.73 m(2) at 1 year. Preoperative mean contralateral normal kidney volume was 225.7 mL in the simple nephrectomy group and 180.1 mL in the radical nephrectomy group (P < 0.001). The contralateral normal kidney volume to total normal kidney volume ratio was 0.74 in the simple nephrectomy group and 0.51 in the radical nephrectomy group (P < 0.001). CONCLUSIONS: Preoperative volumetric compensation of the contralateral normal kidney is important to maintain postoperative renal function in patients undergoing nephrectomy.

Prognostic factors after salvage radiotherapy alone in patients with biochemical recurrence after radical prostatectomy.

OBJECTIVES: To evaluate the oncological outcome and to assess prognostic factors of salvage radiotherapy alone in patients with biochemical recurrence after radical prostatectomy. METHODS: We reviewed our single institution, prospectively maintained database of 2043 patients who underwent radical prostatectomy between September 1995 and December 2011. In this cohort, 149 patients who developed biochemical recurrence after radical prostatectomy and received salvage radiotherapy alone after pelvic magnetic resonance imaging were included. Three-dimensional conformal radiotherapy or intensity-modulated radiotherapy was delivered with a median dose of 70.0 Gy (66.0-78.0 Gy) or 67.2 Gy (64.8-70.0 Gy). Kaplan-Meier and Cox regression analyses were carried out. RESULTS: With a median follow up of 82 months (range 20-153 months), 55 patients (36.9%) failed salvage radiotherapy. The 5-year salvage radiotherapy failure-free probability was 53.6%. On multivariate analysis, pre-salvage radiotherapy prostate-specific- antigen ≥ 1.0 ng/mL (P = 0.003, hazard ratio 3.592, 95% confidence interval 1.522-8.579), pathological stage ≥ T3a (P = 0.004, hazard ratio 2.261, 95% confidence interval 1.290-3.833), pathological Gleason score ≥ 7 (P = 0.018, hazard ratio 5.501, 95% confidence interval 1.577-21.221), prostate-specific antigen doubling time < 12 months (P = 0.014, hazard ratio 2.243, 95% confidence interval 1.177-4.275) and no visible lesion on pelvic magnetic resonance imaging (P = 0.016, hazard ratio 2.068, 95% confidence interval 1.268-3.501) were independent prognostic factors of salvage radiotherapy failure after radical prostatectomy. CONCLUSIONS: Pre-salvage radiotherapy prostate-specific antigen ≥ 1.0 ng/mL, pathological stage ≥ T3a, pathological Gleason score ≥ 7, prostate-specific antigen doubling time < 12 months and no visible lesion on pelvic magnetic resonance imaging are prognostic factors of salvage radiotherapy failure after radical prostatectomy. We should consider additional treatment in patients with these factors for favorable outcomes.

Tpl2 induces castration resistant prostate cancer progression and metastasis.

Progression to metastatic castration resistant prostate cancer (CRPC) is the major lethal pathway of prostate cancer (PC). Herein, we demonstrated that tumor progression locus 2 (Tpl2) kinase is the fundamental molecule provoking progression and metastasis of CRPC. Tpl2 upregulates CXCR4 and focal adhesion kinase (FAK) to activate CXCL12/CXCR4 and FAK/Akt signalling pathway. Consequently, epithelial-mesenchymal transition (EMT) and stemness of androgen depletion independent (ADI) PC cells are induced, which is dependent on the kinase activity of Tpl2. In vitro, proliferation, clonogenicity, migration, invasion and chemoresistance of ADI PC cells were enhanced by Tpl2. In vivo, Tpl2 overexpression and downregulation showed significant stimulatory and inhibitory effects on tumorigenic and metastatic potential of ADI PC cells, respectively. Moreover, the prognostic effects of Tpl2 and expressional correlation between Tpl2 and EMT-related molecules/CXCR4 were validated in clinical PC databases. Since Tpl2 exerts metastatic progression promoting activities in CRPC, Tpl2 could serve as a novel therapeutic target for metastatic CRPC.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PURPOSE: We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. MATERIALS AND METHODS: We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. RESULTS: Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). CONCLUSIONS: Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration.

Clinical significance of prognosis using the neutrophil-lymphocyte ratio and erythrocyte sedimentation rate in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma.

OBJECTIVES: To evaluate the clinical significance of preoperative erythrocyte sedimentation rate (ESR) and neutrophil-lymphocyte ratio (NLR) as prognostic factors in patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A total of 410 patients were retrospectively reviewed. An elevated NLR was defined as ≥2.5 and a normal ESR was considered to be in the range of 0-22 mm/h in men and 0-27 mm/h in women. Patients were divided into three groups: those with ESR and NLR in the normal range (group 0, n = 168), those with either elevated ESR or elevated NLR (group I, n = 169), and those with both elevated ESR and elevated NLR (group II, n = 73). RESULTS: The median patient age was 64 years and the median follow-up duration was 40.2 months. In all, 35.6 and 41.2% of patients had elevated NLRs and ESRs, respectively. Group II was associated with advanced tumour status in terms of size, grade, stage, lymph node and margin status (P < 0.05). Preoperative ESR (hazard ratio [HR] 1.784, 95% confidence interval [CI] 1.173-2.712), NLR (HR 1.704, 95% CI 1.136-2.556), and prognostic grouping (HR 2.285, 95% CI 1.397-3.737 for group I; HR 2.962, 95% CI 1.719-5.102 for group II) were independent predictors of progression-free survival (PFS) in the multivariate model (P < 0.05). Prognostic grouping was also an independent prognostic factor for cancer-specific survival (CSS) and overall survival (OS). Time-dependent area under the receiver-operating characteristic curves showed that NLR plus ESR had a greater diagnostic value than NLR alone regarding oncological outcomes (P < 0.05). CONCLUSIONS: Prognostic grouping using ESR and NLR was identified as an independent prognostic marker in patients with UTUC. The addition of ESR improved the prognostic value of NLR alone in predicting oncological outcomes. The combination of preoperative ESR and NLR might be a new prediction tool in patients with UTUC after radical nephroureterectomy.

Measurement of renal function in a kidney donor: a comparison of creatinine-based and volume-based GFRs.

OBJECTIVE: We aimed to evaluate the performance of various GFR estimates compared with direct measurement of GFR (dGFR). We also sought to create a new formula for volume-based GFR (new-vGFR) using kidney volume determined by CT. MATERIALS AND METHODS: GFR was measured using creatinine-based methods (MDRD, the Cockcroft-Gault equation, CKD-EPI formula, and the Mayo clinic formula) and the Herts method, which is volume-based (vGFR). We compared performance between GFR estimates and created a new vGFR model by multiple linear regression analysis. RESULTS: Among the creatinine-based GFR estimates, the MDRD and C-G equations were similarly associated with dGFR (correlation and concordance coefficients of 0.359 and 0.369 and 0.354 and 0.318, respectively). We developed the following new kidney volume-based GFR formula: 217.48-0.39XA + 0.25XW-0.46XH-54.01XsCr + 0.02XV-19.89 (if female) (A = age, W = weight, H = height, sCr = serum creatinine level, V = total kidney volume). The MDRD and CKD-EPI had relatively better accuracy than the other creatinine-based methods (30.7% vs. 32.3% within 10% and 78.0% vs. 73.0% within 30%, respectively). However, the new-vGFR formula had the most accurate results among all of the analyzed methods (37.4% within 10% and 84.6% within 30%). CONCLUSIONS: The new-vGFR can replace dGFR or creatinine-based GFR for assessing kidney function in donors and healthy individuals. KEY POINTS: • Accurate prediction of GFR is crucial in kidney donors. • DTPA is accurate but costly, invasive, and clinically difficult to apply. • Volume-based GFR estimation performs as well as the Cr-based method. • New volume-based GFR estimation performs better among GFR estimation formulas.