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1.

Purpose

Overexpression of Caveolin-1 has been associated with cancer growth, migration, and metastases in several malignancies, but only few data are available on its role in bladder cancer (BCa). The aim of this study is to validate Caveolin-1 as a prognosticator of recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in a large cohort of patients treated with radical cystectomy (RC) for BCa.

Methods

Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray from 424 patients treated with RC for UCB at a single institution. Caveolin-1 was considered overexpressed when at least 50% of the tumor cells stained positively. Univariable and multivariable Cox proportional hazards regression models were used to assess the association of Caveolin-1 expression with RFS, OS, and CSS.

Results

Overexpression of Caveolin-1 was observed in 116 (27.4%) patients and was associated with lymph node metastasis (P = 0.003). Median follow-up for patients alive at last follow-up was 129 months (interquartile range [IQR]: 82–178). Patients with overexpression of Caveolin-1 had significant worse RFS, OS, and CSS compared to those with normal expression (log-rank test, P = 0.008, P = 0.001, and P = 0.005, respectively). At multivariable analyses that adjusted for the effects of standard clinicopathologic features, Caveolin-1 remained associated with OS (hazard ratio = 1.47, P = 0.002) and CSS (hazard ratio = 1.42, P = 0.03). Conversely, no association with RFS was found (P = 0.1). Addition of Caveolin-1 in a model for prediction of survival did not improve the accuracy of the prognostic model. Actually, C-index did not differ among models with or without Caveolin-1 (0.72 for a model predicting RFS, 0.65 for OS, and 0.71 for CSS).

Conclusions

Caveolin-1 is overexpressed in one-third of patients with BCa treated with RC. Overexpression of Caveolin-1 is significantly associated with OS and CSS, but not with RFS, in patients with BCa treated with RC. However, it is not clinically useful as it does not improve upon the predictive accuracy of survival achieved by pathologic variables alone.  相似文献   

2.

Objective

The purpose of this study was to investigate the correlation between the controlling nutritional status (CONUT) score and survival of patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy (RNU).

Methods and materials

We retrospectively enrolled 107 patients. CONUT score was calculated based on the serum albumin concentration, lymphocyte count, and total cholesterol concentration. Patients were classified into 2 groups based on CONUT score. Relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU were compared between the 2 groups, and predictors of survival were analyzed using Cox proportional hazards regression models.

Results

For CONUT score, the area under the curve was 0.588 and the optimal cutoff value was 3. Twenty-four patients (22.4%) had high CONUT scores. The patients with high CONUT scores had significantly shorter 5-year RFS, CSS, and OS than did those with low CONUT scores (RFS: 50.1% vs. 66.0%; CSS: 28.1% vs. 71.7%; OS: 26.4% vs. 66.8%; all P<0.05). Results of the multivariable analysis, after adjustment for factors such as pT stage, pN stage, tumor grade, presence of lymphovascular invasion, and C-reactive protein level, revealed that CONUT score was an independent predictor of CSS (hazard ratio [HR] = 5.44, P = 0.0016) and OS (HR = 2.90, P = 0.0214) and showed marginal significance for predicting RFS (HR = 2.26, P = 0.0581).

Conclusions

Preoperative CONUT score helps predict survival in patients with localized urothelial carcinoma of the upper urinary tract treated with RNU.  相似文献   

3.

Purpose

Accumulating evidence indicates that CXC chemokine receptor 6 (CXCR6) has a crucial role in cancer development and progression, however, its role in clear cell renal cell carcinoma (ccRCC) remains obscure. The aim of this study is to investigate the prognostic value of CXCR6 expression in patients with ccRCC following surgery.

Materials and methods

This study retrospectively included 239 patients with ccRCC who underwent nephrectomy and had paraffin tissue available at a single center. CXCR6 expression in tumor tissue was evaluated by immunohistochemistry and its associations with overall survival (OS) and recurrence-free survival (RFS) were investigated.

Results

A total of 47.3% tumors were considered as high expression of CXCR6, which was significantly associated with the male sex (P = 0.003) and high Fuhrman grade (P<0.001). A high expression of CXCR6 indicated a reduced OS (P<0.001) and RFS (P = 0.007). Multivariate analysis demonstrated that CXCR6 expression was an independent prognostic factor of OS (hazard ratio = 2.604; 95% CI: 1.338–5.068; P = 0.005) and RFS (hazard ratio = 1.957; 95% CI: 1.065–3.595; P = 0.031). Subgroup analysis found that CXCR6 expression could differentiate survival risks among patients with high-risk disease. Moreover, a nomogram integrating CXCR6 expression and traditional clinical and pathologic features was established and predicted postsurgical recurrence-risk well at 3- and 5-year.

Conclusions

The expression of CXCR6 in tumor tissue may serve as a potential prognostic biomarker to refine clinical prognosis prediction combined with traditional clinical and pathological analysis for patients with ccRCC after surgery.  相似文献   

4.

Objective

To validate the clinical and prognostic significance of our proposed pN3 subclassification in penile cancer.

Materials and methods

A retrospective analysis of 509 patients with penile cancer undergoing partial, total penectomy or inguinal lymphadenectomy or pelvic lymphadenectomy at Sun Yat-sen University Cancer Center was reevaluated by pathologists. pN3 stage was subclassified into pN3a (extranodal extension of any inguinal lymph node [LN] metastasis only) and pN3b (pelvic LN metastasis). The t test and chi-square test were applied to assess the comparability of pN3a and pN3b with clinicopathologic features. Univariable and multivariable statistical analyses were used to evaluate prognostic effect with cancer-specific survival.

Results

Among 509 patients, 71 patients with pN3 stage cancer were divided into 39 with pN3a and 32 with pN3b. The median number of LNs removed and the number of positive LNs were 27 and 3, respectively. The 3-year cancer-specific survival in pN3a and pN3b groups was significantly different at 47.9% and 28.6% (P = 0.003). In multivariable analysis, pN3 subclassification was an independent predictor for cancer-specific mortality (hazard ratio = 2.77; 95% CI: 1.170–6.558; P = 0.02). Adding pN3 subclassification to a multivariable model including pT stage, tumor grade, side involvement, lymphovascular invasion, number of positive LNs, and adjuvant therapy increased predictive accuracy for cancer-specific mortality from 0.665 to 0.695 (P<0.001).

Conclusions

Subclassification helps better distinguish patients with pN3 penile cancer with increased risk of disease progression and cancer-related mortality.  相似文献   

5.

Objective

To investigate contemporary survival trends in penile cancer.

Methods

The National Cancer Database was queried for men with penile cancer diagnosed between 1998 and 2009. Patient, tumor, treatment, and facility characteristics were obtained. Overall survival (OS) was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression model for all cases and stratified by stage.

Results

A total of 8,122 cases of penile cancer were reported from 1998 to 2009 in the National Cancer Database. Complete staging, survival, and covariate data were available for 5,043 cases. The estimated crude 5-year OS for the entire cohort was 61.0%. For all patients, no significant differences in crude 5-year OS were detected between 2006 to 2009 and 2002 to 2005 compared to 1998 to 2001. On multivariable analysis, OS did not significantly differ across all eras. Regional lymph node dissection was associated with improved OS (hazard ratio [HR] = 0.777, P ≤ 0.0001). In patients who underwent lymph node dissection, dissection of ≥8 nodes significantly improved survival (HR = 0.672; P = 0.0011). Additional modeling stratified by stage revealed that OS for stage II cancers increased significantly in 2006 to 2009 compared to 1998 to 2001 (HR = 0.714; P = 0.0034).

Conclusions

Survival in penile cancer has remained unchanged as a whole and for each stage, except for stage II disease. An improved survival trend was detected in stage II penile cancer. Performing a lymph node dissection, especially extensive dissections, may benefit long-term survival.  相似文献   

6.

Purpose

Galectin-9, a member of the “tandem repeat” type galectins performing as animal lectins with an affinity for β-galactosides, has been well documented to exert crucial functions in immunomodulation, survival, and growth of various tumors. This study aims to reveal the clinical significance of galectin-9 in urothelial carcinoma of the bladder (UCB) postoperatively.

Materials and methods

We retrospectively included 202 patients with UCB who underwent radical cystectomy at a single institute from 2002 to 2014. Galectin-9 expression was assessed by immunohistochemistry on tissue microarrays. The Kaplan-Meier method was conducted to plot survival curves. Prognostic nomograms were constructed via integrating all the independent indicators from multivariate Cox analysis for recurrence-free survival (RFS) and cancer-specific survival (CSS). In addition, we evaluate whether patients with increased or decreased galectin-9 expression might benefit from adjuvant chemotherapy.

Results

Low galectin-9 expression was significantly correlated with lymphovascular invasion (P = 0.002), early recurrence (P = 0.010), and short CSS (P = 0.002). Furthermore, multivariate analysis identified galectin-9 expression as a potential independent indicator for RFS (hazard ratio = 0.62; 95% CI: 0.40–0.95; P = 0.030) and CSS (hazard ratio = 0.46; 95% CI: 0.26–0.81; P = 0.008). Moreover, the benefit associated with adjuvant chemotherapy was superior among galectin-9 low patients than among galectin-9 high patients (P = 0.014).

Conclusions

Expression of galectin-9 is an independent prognostic factor for RFS and CSS in patients with UCB. Evaluation of galectin-9 expression may predict the benefit from adjuvant chemotherapy.  相似文献   

7.

Introduction

The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib.

Materials and methods

In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect.

Results

HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival.

Conclusion

HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation.  相似文献   

8.

Purpose

To externally evaluate a preoperative points system and a preoperative nomogram, both created to assess time to death after cytoreductive nephrectomy (CN).

Materials and methods

We identified 298 patients who underwent CN at our institution, a tertiary cancer center, between 1989 and 2015. To validate the points system, we compared reported overall survival (OS) for each criterion to observed OS in our cohort. To evaluate the nomogram, we prognosticated risk of death at 6 months after surgery for 280 patients with sufficient follow-up in our cohort and evaluated discrimination using area under the curve (AUC) and calibration. Decision curve analysis was performed to assess clinical utility of the nomogram.

Results

Significant differences in OS were observed between patients with and without 5 of 7 criteria on univariate analysis: low albumin (P<0.0001), high lactate dehydrogenase (P = 0.002), liver metastasis (P = 0.004), retroperitoneal lymphadenopathy (P = 0.002), and supradiaphragmatic lymphadenopathy (P = 0.019). Discrimination from the preoperative model, predicting death within 6 months of surgery was lower in our cohort (AUC = 0.65, 95% CI: 0.52–0.79) than the original publication (AUC = 0.76). Decision curve analysis demonstrated little benefit for applicability.

Conclusions

Five previously defined risk factors are predictive of decreased OS after CN in our cohort. We found lower discrimination using the preoperative model and minimal clinical utility according to decision analysis in our study cohort. These findings suggest the need for improved models to aid patient stratification and consequent treatment choice.  相似文献   

9.

Objectives

Recent studies have demonstrated that up-front docetaxel combined with androgen deprivation therapy (ADT) prolongs survival in some patients with metastatic hormone-naïve prostate cancer (mHNPC). However, new biomarkers for selecting personalized treatment strategies for mHNPC are warranted. We evaluated the value of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression as a prognosticator in men with mHNPC.

Methods and materials

A total of 48 men with mHNPC diagnosed from 2003 to 2009 were enrolled in this study. Prostate cancer tissues obtained by needle biopsies were immunohistochemically stained for LMW-PTP. Correlations between LMW-PTP expression and clinicopathological characteristics were then assessed.

Results

At the time of analysis, 29 (60.4%) patients were alive, whereas 15 (31.3%) and 4 (8.3%) died of prostate cancer and nonprostate cancer, respectively. Of these, 29 (60.4%) had low LMW-PTP expression and 19 (39.6%) had high expression. Median overall survival (OS) for patients with high LMW-PTP expression was not reached and that for patients with low LMW-PTP expression was 23.8 months. High LMW-PTP expression was significantly correlated with a shorter OS compared with low LMW-PTP expression (P = 0.01). Moreover, multivariate analysis showed that Gleason score (≥8 vs.≤7; HR = 5.8, 95% CI: 1.3–26.5, P = 0.02) and LMW-PTP expression (high vs. low; HR = 2.7, 95% CI: 1.0–7.2, P = 0.04) were independent prognostic factors for OS.

Conclusions

LMW-PTP is a potential biomarker to predict OS in patients with mHNPC.  相似文献   

10.
11.

Purpose

To establish prognostic genomic biomarkers for patients with metastatic clear cell renal cell carcinoma (ccRCC).

Materials and methods

We identified 60 patients who presented with metastatic ccRCC at our institution between 2001 and 2015 and had genomic sequencing on their primary tumor. We pooled these patients with 107 other patients with the same inclusion criteria from three well-known public databases. Five commonly mutated genes were chosen for analysis: VHL, PBRM1, BAP1, SETD2, and KDM5C. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test was used for comparisons between groups.

Results

Median OS in the cohort was 2.5 years. Higher Fuhrman grade was associated with decreased median OS (P<0.001). Mutations in SETD2 (P = 0.027) and KDM5C (P = 0.019) were associated with reduced risk of death (hazard ratio [HR] = 0.58 [95% CI: 0.35–0.94] and HR = 0.43 [95% CI: 0.22–0.85], respectively). BAP1 mutations (P = 0.008) were associated with increased risk of death (HR = 1.81 [95% CI: 1.16–2.83]). There were significantly more female patients with a BAP1 mutation than females in the overall cohort (P = 0.001).

Conclusions

Mutations in BAP1 negatively affected OS, whereas SETD2 and KDM5C mutations were associated with prolonged OS in our pooled cohort of 167 patients with metastatic ccRCC. Our results expand upon efforts at understanding genomic biomarkers in localized disease. Those efforts set the stage for our novel investigation examining associations of select recurrent somatic mutations in stage IV patients with ccRCC.  相似文献   

12.

Objectives

To describe the effects of cytoreductive nephrectomy (CN) on the natural course of metastatic renal cell carcinoma (mRCC). CN appears to stabilize metastatic lesions in mRCC in a subgroup of patients and we hypothesize that systemic treatment might be deferred in these patients with stable disease after CN.

Subjects and methods

Overall, 45 patients with mRCC who underwent CN and subsequent oncologic follow-up were included in this retrospective, single-center analysis. After CN, patients were followed at least every 3 months with clinical evaluation, contrast-enhanced computerized tomography scan of chest and abdomen, with additional imaging if needed. At 3 months, patients were radiographically evaluated and categorized into nonresponders (death or progression) or responders (stable disease or remission). Kaplan-Meier and Cox proportional hazards regression statistics were used to describe prognostic factors for overall survival (OS) and systemic therapy–free survival (STFS).

Results

Median OS was 31(3–121) months. Further, 24 (53.3%) and 21 (46.7%) patients were classified as responders and nonresponders at 3 months, respectively. Responders had a significant better 2-year OS compared with nonresponders (81.7% vs. 26.5%, P = 0.005). Responders also had a better 2-year STFS (40.3% vs. 6.3%, P = 0.005). On Cox regression analysis, worse OS was found to be associated with low preoperative hemoglobin levels, the absence of postoperative radiographical response, and the presence of non–clear cell pathology. The presence of postoperative radiographical response, normal preoperative lactate dehydrogenase levels, the presence of a single metastasis, and performing metastasis-directed therapy was found to be associated with a longer systemic therapy-free period.

Conclusion

A beneficial oncologic response is observed in approximately half of the patients undergoing CN. Absence of radiographic progression at 3 months is an important marker for OS and STFS. Therefore, systemic treatment might be postponed in selected patients.  相似文献   

13.

Background

Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.

Methods

This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary end point was the objective response rate (ORR). Secondary end points included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives.

Results

Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had>10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with≤10% sarcomatoid histology (P = 0.04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7).

Conclusions

These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation.  相似文献   

14.

Objectives

To investigate the effect of variant histology (VH) on survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma (UTUC) and the effect of adjuvant chemotherapy on the survival of patients with UTUC with VH.

Materials and methods

A total of 452 patients who underwent radical nephroureterectomy for UTUC without neoadjuvant chemotherapy in our institution between 1991 and 2012 were retrospectively analyzed. We performed a comparative analysis between pure UTUC and UTUC with VH groups. The Kaplan-Meier method was used to calculate survival estimates for cancer-specific survival (CSS) and overall survival (OS), and log-rank test was used to conduct comparisons between the groups. Univariate and multivariate Cox-proportional hazard regression analyses were performed to evaluate significant variables associated with CSS and OS.

Results

UTUC with VH was present in 41 (9.1%) patients. UTUC with VH showed aggressive clinicopathological features in comparison with pure UTUC. The Kaplan-Meier curves showed significantly decreased 5-year CSS and OS (both, P<0.001) in UTUC with VH group. Multivariate analysis revealed that VH was an independent predictor of CSS (P<0.001) and OS (P<0.002). The Kaplan-Meier curves also showed significantly decreased 5-year CSS and OS in UTUC with the VH group compared to the pure UTUC group in patients who received adjuvant chemotherapy.

Conclusions

We found that UTUC with VH harbored aggressive biologic features, and VH was an independent prognostic factor for CSS and OS on both univariate and multivariate analyses. In addition, UTUC with VH group had poorer survival outcomes than pure UTUC group in patients who received adjuvant chemotherapy. Consequently, adjuvant treatment modalities other than adjuvant chemotherapy should be considered in this group.  相似文献   

15.

Background

There are currently no methods in clinical use that can detect early systemic dissemination of urothelial tumor cells.

Objective

To evaluate measurement of circulating tumor cells (CTCs) as a biomarker for disseminated disease in patients with advanced bladder cancer.

Design, setting, and participants

Between March 2013 and October 2015, 88 patients were prospectively included in the study: 78 were scheduled for radical cystectomy (RC) ± perioperative chemotherapy and 10 treated with palliative chemotherapy. The CellSearch CTC test was further assessed in this context by investigating expression of epithelial cell adhesion molecule (EpCAM) in primary tumors obtained at cystectomy from an independent cohort of 409 patients.

Outcome measurements and statistical analysis

Presence of CTCs was tested for association with tumor stage, lymph node metastases, metastatic disease on [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cancer-specific and progression-free survival.

Results

CTCs were detected in 17/88 patients (19%). In 61 patients who underwent FDG-PET-computed tomography (CT), a statistically significant association with presence of CTCs was found for radiological metastatic disease but not for normal PET-CT results (12/35 [34%] vs. 2/26 [8%], P = 0.014). After a median follow-up time of 16.5 months (95% CI: 9.6–21.4), presence of CTCs was associated with an increased risk of progression among patients treated with RC with or without perioperative chemotherapy (n = 75, P = 0.049). A multivariate analysis adjusted for clinical tumor stage, clinical lymph node status, and age showed that CTCs were an independent marker of progression (n = 75; hazard ratio = 2.78; 95% CI: 1.005–7.69; P = 0.049) but not of cancer-specific death (P = 0.596). In 409 cystectomised patients, more than 392 (96%) of the bladder tumors expressed EpCAM.

Conclusions

CTCs were present in 19% of patients with advanced urothelial tumors and were associated with metastatic disease on FDG-PET-CT and with increased risk of disease progression after RC. A significant portion of urothelial cancer cells do express EpCAM and can thus be identified using EpCAM-antigen–based CTC detection methods.  相似文献   

16.

Objective

To assess the relationship of race and margin status among patients undergoing robotic partial nephrectomy (RPN) for T1 renal tumors from a contemporary population-based cohort.

Methods

Using the National Cancer Database, we identified patients with localized renal cell carcinoma (RCC) (clinical T1N0M0) who underwent RPN from 2010 to 2013. The primary outcome was positive surgical margins (PSM). Multivariable logistic regression analyses were used to assess the association between race and PSM adjusting for patient clinicopathologic and hospital factors.

Results

Among 12,515 patients undergoing RPN in our cohort, 8.3% had PSM (n = 1,045). When compared to white patients undergoing RPN for T1 RCC with PSM (7.9%), we observed a higher proportion of PSM among African American (AA) (10.8%; P = 0.005) and Hispanic/Latino patients (8.8%; P = 0.005), respectively. On multivariable analysis, AA patients had higher odds of PSM compared to white patients (odds ratio = 1.40; P = 0.008). Other factors associated with higher odds of PSM were treatment at nonacademic centers relative to academic centers (10.4% vs. 6.9%; odds ratio = 1.57; P<0.001).

Conclusions

In this contemporary population-based cohort, AA patients undergoing RPN for localized RCC tumors are at higher risk for PSM. These results suggest potential differences in quality of care and patient selection of RPN by race.  相似文献   

17.

Purpose

Sialic acid-binding immunoglobulin-like lectins (siglecs) family has important functions in tumor progression. The purpose of our study is to figure out the correlation between the expression level of Siglec-8 and prognosis of patients with clear cell renal cell carcinoma (ccRCC), and then to predict the overall survival (OS) via a novel nomogram.

Materials and methods

A group of patients (n = 267) histologically diagnosed with ccRCC from Zhongshan Hospital were included into our study. Immunohistochemistry of Siglec-8 was performed in the tissue microarray, and the staining intensity was divided into high/low according to the median value of the H-score grading. Survival analyses including Kaplan-Meier analyses and Cox regression analyses were performed to evaluate the association between Siglec-8 expression and the survival of patients in different risk groups. Stage, size, grade, and necrosis score and University of California Los Angeles Integrated Staging System score were used in the risk stratification. A nomogram incorporating Siglec-8 and several other clinical parameters was plotted for predicting the 5-year and 8-year OS.

Results

Siglec-8 was observed dominantly on the membrane of tumor cells. The enhanced expression level of Siglec-8 had significant correlation with adverse overall and disease-free survival of patients (P<0.0001 and P = 0.0186, respectively). The association was more significant in patients with lower risk. Cox regression analyses defined Siglec-8 as an independent prognostic factor of OS (P<0.001 for univariate analysis, P = 0.003 for multivariate analysis). The new nomogram integrating Siglec-8 with several traditional prognostic factors proved to be more accurate than conventional prognostic system using tumor node metastasis stage only (Harrell c-index: 0.801, 95% CI: 0.755–0.847 vs. 0.717, 95% CI: 0.662–0.772).

Conclusion

Our study has found that the elevated expression level of Siglec-8 was correlated with poor prognosis of patients with ccRCC. Siglec-8, incorporation with other clinical parameters, could perform better in prediction of patients? OS.  相似文献   

18.

Background

Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC).

Objective

Report long-term outcomes of patients with MIBC treated by TMT.

Design, setting, and participants

Four hundred and seventy-five patients with cT2–T4a MIBC were enrolled on protocols or treated as per protocol at the Massachusetts General Hospital between 1986 and 2013.

Intervention

Patients underwent transurethral resection of bladder tumor followed by concurrent radiation and chemotherapy. Patients with less than a complete response (CR) to chemoradiation or with an invasive recurrence were recommended to undergo salvage radical cystectomy.

Outcome measurements and statistical analysis

Disease-specific survival (DSS) and overall survival (OS) were calculated using the Kaplan-Meier method.

Results and limitations

Median follow-up for surviving patients was 7.21 yr. Five- and 10-yr DSS rates were 66% and 59%, respectively. Five- and 10-yr OS rates were 57% and 39%, respectively. The risk of salvage cystectomy at 5 yr was 29%. In multivariate analyses, T2 disease (OS hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.44–0.75, DSS HR: 0.51, 95% CI: 0.36–0.73), CR to chemoradiation (OS HR: 0.61, 95% CI: 0.46–0.81, DSS HR: 0.49, 95% CI: 0.34–0.71), and presence of tumor-associated carcinoma in situ (OS HR: 1.56, 95% CI: 1.17–2.08, DSS HR: 1.50, 95% CI: 1.03–2.17) were significant predictors for OS and DSS. When evaluating our cohort over treatment eras, rates of CR improved from 66% to 88% and 5-yr DSS improved from 60% to 84% during the eras of 1986–1995 to 2005–2013, while the 5-yr risk of salvage radical cystectomy rate decreased from 42% to 16%.

Conclusions

These data demonstrate high rates of CR and bladder preservation in patients receiving TMT, and confirm DSS rates similar to modern cystectomy series. Contemporary results are particularly encouraging, and therefore TMT should be discussed and offered as a treatment option for selected patients.

Patient summary

Tri-modality therapy is an alternative to radical cystectomy for patients with muscle-invasive bladder cancer, and is associated with comparable long-term survival and high rates of bladder preservation.  相似文献   

19.

Objectives

The aim of the study was to evaluate the expression of TMEM67 in urothelial carcinoma of the bladder (UCB) tissues and to determine the potential relevance between the expression of TMEM67 and prognosis of UCB.

Material and methods

In this study, the expression of TMEM67 mRNA was performed by quantitative real-time PCR in 80 UCB and 54 noncancerous tissues. The expression of TMEM67 protein was identified by immunohistochemistry and western blotting. Chi-square test was conducted to verify the relevance between the expression of TMEM67 and clinical parameters. Kaplan-Meier survival analysis was demonstrated between high or low expression level of TMEM67 mRNA and recurrence-free survival probability. Cox regression analysis was conducted to evaluate the relevance between the expression of TMEM67 and the prognosis in UCB.

Results

Low expression of TMEM67 mRNA and protein was detected in most of UCB tissues using quantitative real-time polymerase chain reaction and western blotting, compared with noncancerous tissues. Low expressions of TMEM67 were associated with TNM stage, grade, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that the low expression of TMEM67 mRNA had significantly shorter recurrence-free survival probability (P = 0.018). Cox regression analysis confirmed that low expression of TMEM67 mRNA predicted poor prognosis of patients with UCB (HR = 2.950, P = 0.029, 95% CI: 1.1167.796).

Conclusions

TMEM67 expression is low in UCB tissues, and the TMEM67 low expression predicted poor prognosis of patients with UCB.  相似文献   

20.

Purpose

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model has been designed for prognostification in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. One factor is neutrophil count; however, increasing evidence has suggested the superiority of neutrophil-to-lymphocyte ratio (NLR) for predicting outcome. In this study, we evaluate the prognostic effect of NLR levels on patients with mRCC treated with targeted therapy, and then we compare the predictive accuracy of the IMDC risk model and its modified one by using NLR, instead of neutrophil count.

Patients and method

A total of 277 patients are included for the analysis. All patients underwent targeted therapies and associated outcome are assessed using multivariate analysis.

Results

Pretreatment NLR levels are elevated in 30.3% and 23.1% of patients in the first-line and subsequent second-line setting, respectively. Kaplan-Meier curves reveal that elevated pretreatment NLR is significantly associated with poor overall survival (OS) since first-line (P<0.001) and second-line targeted therapy administration (P<0.001). Also, multivariate analyses show that elevated pretreatment NLR is an independent predictor for poor OS since first-line and second-line targeted therapy administration. The addition of NLR to the IMDC risk model, instead of neutrophil count, significantly improves the predictive accuracy for OS, and estimated gain is 1.7% and 6.2% in first-line and second-line targeted therapy, respectively.

Conclusion

Changes in NLR levels could be predictive for prognosis in patients with mRCC treated with first-line and second-line targeted therapy. The addition of NLR significantly improves the predictive accuracy of the IMDC risk model in the first-line and subsequent second-line setting.  相似文献   

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