Prognostic value of preoperative radiographic perinephric fat features in renal cell carcinoma patients undergoing surgery.

BACKGROUND: We aimed to assess the prognostic importance of perinephric fat features in images of patients with non-metastatic renal cell carcinoma (RCC) undergoing surgery. METHODS: We enrolled RCC patients who underwent surgical treatment between 2011 and 2019. Two characteristics, including perinephric fat thickness and perinephric fat stranding, were evaluated using preoperative computed tomography or magnetic resonance images. The association between perinephric fat characteristics and disease progression was examined by Kaplan-Meier survival analysis and Cox regression model. RESULTS: In a multivariate Cox proportional hazards model adjusting for tumor stage, intratumoral necrosis, and neutrophil-to-lymphocyte ratio, we found that patients in the thin perinephric fat group (<1 cm) had a poorer progression-free survival (PFS) compared to the thick perinephric fat group (≥1 cm) (HR 2.8; 95% CI 1.175-6.674, p = 0.02). Additionally, the fat stranding group had a poorer PFS than the non-stranding group (HR 3.852; 95% CI 1.082-13.704, p = 0.037). The non-stranding with thick perinephric fat group exhibits the highest cumulative PFS while the stranding with thin perinephric fat group has the lowest cumulative PFS. In receiver operating characteristic curve analysis, combing these two perinephric fat characteristics with tumor stage can achieve a better discriminatory power than tumor stage alone. CONCLUSIONS: Our study indicates that the evaluation of image-based perinephric fat features is a simple, straightforward, reproducible tool for predicting RCC prognosis and may assist in preoperative risk stratification.

The Systemic Immune-Inflammation Index (SII) Increases the Prognostic Significance of Lymphovascular Invasion in Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy.

Purpose: Lymphovascular invasion (LVI) and systemic immune-inflammation index (SII) both have been proved to correlate with oncologic outcomes in upper tract urothelial carcinoma (UTUC). We hypothesize that integrating SII with LVI may be an aid for risk-stratification of prognosis. This study aimed to evaluate the prognostic significance of combined SII and LVI in patients with localized UTUC. Patients and Methods: A retrospective analysis of clinicopathological data of 554 UTUC patients who underwent radical nephroureterectomy (RNU) was conducted. The SII was calculated using the equation (preoperative serum neutrophil*platelet/lymphocyte). Use of Kaplan-Meier analyses and Cox proportional hazards models were to evaluate associations of combining SII and LVI with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Furthermore, receiver operating characteristic (ROC) analysis was applied to estimate predictive ability of combining SII and LVI for oncological outcomes. Results: Positive LVI was significantly associated with advanced stage, high grade, necrosis, lymph node metastasis, and high-level SII. Positive LVI and high-level SII co-existence was significantly associated with unfavorable OS, CSS, and PFS in Kaplan-Meier analyses (all p < 0.001) and was an independent indicator of OS, CSS, and PFS (HR [95% CI]: 3.918 [2.168-7.078], 5.623 [2.679-11.801], 3.377 [2.138-5.334]), respectively) in multivariate analyses. Furthermore, adding LVI and SII to a model that included standard pathologic predictors exhibited a better ability to predict survival in ROC analysis. Conclusion: The integration of SII and LVI was demonstrated to be a potential factor of poor outcomes in patients with localized UTUC. Notably, the combined use of LVI and SII can be a feasible and complementary factor to TNM staging in the prognostic assessment of UTUC patients in clinical practice. The validity of combination of the two markers would be considered in future prospective studies to evaluate its usefulness in staging and application of post-operative chemo or immunotherapy.

Risks of Carotid Artery Stenosis and Atherosclerotic Cardiovascular Disease in Patients with Calcium Kidney Stone: Assessment of Systemic Inflammatory Biomarkers.

(1) Background: To assess the clinical significance of preoperative inflammatory biomarkers combined with atherosclerotic cardiovascular disease (ASCVD) risk score to evaluate carotid artery stenosis in patients with calcium kidney stones; (2) Methods: We conducted a prospective observational case-control study, enrolling 74 patients with calcium kidney stones and 66 age- and sex-matched healthy controls. We calculated the inflammatory biomarkers including the neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI). An ultrasound of the carotid arteries was performed on all participants to identify the severity of the stenosis; (3) Results: All inflammatory biomarkers and the severity of carotid artery stenosis were higher in the calcium kidney stone group than in controls. After stratification of ASCVD, inflammatory biomarkers and carotid artery stenosis severity were still significantly higher in the calcium kidney stone group. Multivariate analyses showed that calcium kidney stones significantly increased the risk of ASCVD and carotid artery stenosis. In multivariate linear logistic regression analyses, calcium kidney stone and ASCVD score had a significant association with carotid artery occlusion, but SIRI did not; (4) Conclusions: Calcium kidney stone is associated with higher levels of inflammatory biomarkers and carotid artery stenosis. Calcium kidney stone is associated with higher levels of inflammatory biomarkers and carotid artery stenosis.

Pre­existing renal insufficiency synchronous with high preoperative neutrophil­to­lymphocyte ratio as a risk factor of intravesical recurrence in patients with pure upper tract urothelial carcinoma after radical nephroureterectomy.

The present study aimed to evaluate the influence of pre-treatment neutrophil-to-lymphocyte ratio (NLR) on bladder recurrence in patients with impaired renal function following radical nephrouretectomy (RNU) to treat pure upper tract urothelial carcinoma (UTUC). Retrospective data of 362 patients with pure UTUC who underwent RNU between 2008 and 2019 were analyzed. Kaplan-Meier analyses were performed to evaluate the association of preoperative NLR and estimation of the glomerular filtration rate (eGFR) with intravesical recurrence-free survival (IVRF). Furthermore, multivariate analyses were conducted to determine independent factors for predicting IVRF. In the retrospective cohort study of 362 patients, 103 patients (28%) had intravesical recurrence in a median follow-up of 50.1 months; among those, 85 (83%) developed bladder recurrence within two years after RNU. The Kaplan-Meier analysis indicated that patients exhibiting lower eGFR and higher NLR showed significantly poor IVRF rates (P=0.044). The simultaneous presence of eGFR <45 and NLR >3.8 was an independent factor for the shorter IVRF time in multivariate analysis with Cox's proportional hazards model. Most intravesical recurrences occurred within two years after RNU, particularly in pre-existing poor eGFR patients with preoperative high NLR. Moreover, pre-existing moderate to severe CKD synchronous with pre-operative NLR >3.8 was demonstrated as an independent factor for subsequent bladder recurrence in patients with pure UTUC following RNU. Therefore, such high-risk patients ought to be provided with close bladder monitoring during the follow-up.

Low Preoperative Mean Platelet Volume/Platelet Count Ratio Indicates Worse Prognosis in Non-Metastatic Renal Cell Carcinoma.

OBJECTIVES: Multiple blood parameters are used to determine the prognosis of renal cell carcinoma (RCC). Mean platelet volume/platelet count (MPV/PC) ratio is related to disease progression in various cancers. Our study tried to evaluate the prognostic value of the MPV/PC ratio in RCC patients who underwent surgery. METHODS: We retrospectively reviewed 89 patients who underwent radical or partial nephrectomy for RCC in a single institution. Baseline characteristics and MPV/PC ratios were analyzed. The optimal cut-off value of the MPV/PC ratio was determined by a receiver operating characteristic (ROC) curve, and our patients were divided into low and high MPV/PC ratio groups. The Kaplan-Meier survival curve and Cox proportional hazards model were applied for progression-free survival (PFS) and overall survival (OS) analyses. Harell's C-index was used to compare the prognostic values of the MPV/PC ratio, MPV and PC. RESULTS: Lower MPV/PC ratios were correlated with more advanced tumor stages and worse outcomes. The optimal cut-off value of the preoperative MPV/PC ratio was 0.034 (sensitivity 84.6%, specificity 56.6%). The Kaplan-Meier survival curve revealed that low MPV/PC ratios were associated with worse PFS (p = 0.007) and OS (p = 0.017). Multivariate analysis showed that low MPV/PC ratios were an independent unfavorable factor for PFS (p = 0.044) and OS (p = 0.015). Harell's C-indexes showed that the prognostic value of the MPV/PC ratio was significantly better than MPV and PC (p < 0.001). CONCLUSION: Low MPV/PC ratios are an independent, unfavorable risk factor for disease progression and overall survival in patients undergoing surgery for RCC.

Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors.

External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving sphincteric BoNT-A injections for refractory EUS dysfunction were retrospectively reviewed. A comparison of the baseline clinical, urodynamic parameters and the treatment responses were made for patients with different EUS dysfunctions. A total of 106 females were included. Significantly increased detrusor overactivity, detrusor contracting pressure and the bladder outlet obstruction index with decreased urge sensation were noted in patients diagnosed with dysfunctional voiding or detrusor sphincter dyssynergia comparing to those diagnosed with poor relaxation of the external urethral sphincter. The average subjective improvement rate was 67% for the injection. The therapeutic effect was not affected by the type of EUS dysfunction. The multivariate analysis revealed that bladder neck narrowing and catheterization history were predictive of negative outcomes. There is a distinct urodynamic presentation for each type of female EUS dysfunction. Sphincteric BoNT-A injection provides a good therapeutic outcome for refractory EUS dysfunction. A narrowing bladder neck and a history of catheterization suggest poor therapeutic outcomes.

Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma.

OBJECTIVES: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan-Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes. RESULTS: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p < 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p < 0.001). CONCLUSIONS: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans.

Combination of Platelet-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio as a New Promising Prognostic Factor in Upper Tract Urothelial Carcinoma With Large Tumor Sizes > 3 cm.

PURPOSE: The purpose of this study was to evaluate the prognostic values of pathological tumor size and preoperative blood-based inflammation biomarkers, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), in upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: From 2007 to 2017, retrospective data of 449 patients with UTUC who underwent radical nephroureterectomy were assessed. Use of Kaplan-Meier and univariable/multivariable analyses evaluated the effect of preoperative blood-based inflammation biomarkers on overall (OS), cancer-specific (CSS), and progression-free survival (PFS) in pathological tumor sizes > and ≤3 cm. RESULTS: Kaplan-Meier analyses showed that high-level NLR, PLR, or MLR had significantly shorter OS, CSS, and PFS for tumor sizes >3 cm (all P < .05), but not for ≤3 cm. For UTUCs with tumor sizes >3 cm, multivariable analyses showed simultaneously high-level PLR and MLR to be independent predicators of poor OS, CSS, and PFS (all P < .05). Moreover, receiver operating characteristic (ROC) analyses revealed that the predictive accuracy of the combination of PLR and MLR for OS, CSS, and PFS with the area under the ROC curve of 0.836, 0.871, and 0.806, respectively, in tumor sizes >3 cm (all P < .001). CONCLUSIONS: Our study demonstrated that a high-level PLR and MLR can serve as an independent predicator of worse outcomes in UTUCs with tumor sizes >3 cm. This combination can clinically help enhance the prognostic discrimination of UTUCs with tumor sizes >3 cm and further may guide physicians in selecting patients for postoperatively systemic chemotherapy.

Combination of the Preoperative Systemic Immune-Inflammation Index and Monocyte-Lymphocyte Ratio as a Novel Prognostic Factor in Patients with Upper-Tract Urothelial Carcinoma.

BACKGROUND: This study aimed to evaluate the clinical significance of the preoperative systemic immune-inflammation index (SII) combined with the monocyte-lymphocyte ratio (MLR) for patients with upper-tract urothelial carcinoma (UTUC). METHODS: The clinical data of 424 patients who underwent radical nephroureterectomy from January 2007 to June 2017 were analyzed. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate associations of preoperative systemic immune-inflammatory biomarkers with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Moreover, logistic regression preoperative models were applied to predict advanced disease. RESULTS: Multivariate analyses showed that SII significantly influenced both OS and CSS (both P < 0.05), whereas MLR exhibited the most significant association with OS (P = 0.008). In particular, simultaneously high SII and MLR values correlated significantly with OS, CSS, and PFS (all P < 0.05). Logistic regression preoperative models showed that the combination of high SII and high MLR was a significant predictor of non-organ-confined UTUC (P = 0.001). Furthermore, Kaplan-Meier analysis showed that the combination of high SII and high MLR was significantly linked with poor OS, CSS, and PFS in non-organ-confined UTUC (all P < 0.05). CONCLUSION: The study reviewed serum inflammation biomarkers in a subset of patients with UTUC and demonstrated the ability of combined SII and MLR to predict disease progression and survival. Patients with both high SII and high MLR were significantly more likely to have non-organ-confined disease and poor survival outcomes.

Concurrent Preoperative Presence of Hydronephrosis and Flank Pain Independently Predicts Worse Outcome of Upper Tract Urothelial Carcinoma.

OBJECTIVES: To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma. METHODS: In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated. RESULTS: Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis (P = 0.005 and P = 0.026, respectively) and in patients with flank pain (P < 0.001 and P = 0.001, respectively) than those without. However, only simultaneous hydronephrosis and flank pain independently predicted adverse outcome (hazard ratio = 1.98, P = 0.016 for overall survival and hazard ratio = 1.87, P = 0.036 for and cancer-specific survival, respectively) in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis. CONCLUSION: Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When accompanied with flank pain, hydronephrosis represented an independent predictor for worse outcome in patients with upper tract urothelial carcinoma.

Identification of genes differentially expressed during the growth of Bambusa oldhamii.

Bamboos are ecologically and economically important grasses, and are distinguished by their rapid growth. To identify genes associated with bamboo growth, PCR-based mRNA differential display was used to clone genes that were differentially expressed in various tissues of bamboo (Bambusa oldhamii) shoots at different growth stages. In total, 260 different cDNA sequences were obtained. These genes displayed complex expression profiles across the different tissues and growth stages as revealed by a cDNA microarray analysis. Notable among them were genes that were temporally up-regulated or down-regulated in the internode-containing region of rapidly elongating shoots. These genes might participate in the rapid elongation of the bamboo culm. Of the 36 up-regulated and 46 down-regulated genes, 16 genes and 8 genes, respectively, were predicted to encode hypothetical proteins or were unknown sequences. Aside from these, genes involved in hormonal signaling and homeostasis, stress responses, peptide processing and signaling and lignin biosynthesis composed most of the up-regulated genes; genes involved in DNA replication, nucleic acid binding and signal transduction were highly represented among the down-regulated genes. These results suggested that genes associated with plant hormonal signaling and homeostasis, peptide signaling, reactive oxygen species signaling and homeostasis, several stress-related genes and a monocot-specific unknown gene, BoMSP41, play important roles in the elongation of bamboo internodes. Multiple signaling pathways might form a complex interconnected network that controls the rapid growth of this giant grass.

Characterization of a single-stranded DNA-binding protein from Pseudomonas aeruginosa PAO1.

Single-stranded DNA-binding protein (SSB) plays an important role in DNA metabolism, such as in DNA replication, repair, and recombination, and is essential for cell survival. We characterized the single-stranded DNA (ssDNA)-binding properties of Pseudomonas aeruginosa PAO1 SSB (PaSSB) by using fluorescence quenching measurements and electrophoretic mobility shift analysis (EMSA). Analysis of purified PaSSB by gel filtration chromatography revealed a stable tetramer in solution. In fluorescence titrations, PaSSB bound 22-32 nucleotides (nt) per tetramer depending on salt concentration. Using EMSA, we characterized the stoichiometry of PaSSB complexed with a series of ssDNA homopolymers, and the size of the binding site was determined to be 29 ± 1 nt. Furthermore, EMSA results indicated that the dissociation constants of PaSSB for the first tetramer were less than those for the second tetramer. On the basis of these biophysical analyses, the ssDNA binding mode of PaSSB is expected to be noncooperative.