Yuancheng Gou

The prognostic value of C-reactive protein in renal cell carcinoma: A systematic review and meta-analysis

OBJECTIVES C-reactive protein (CRP) has been reported to be associated with poorer prognosis in patients with renal cell carcinoma (RCC); however, conflicting results exist. We conducted a systematic review to evaluate the prognostic value, and a meta-analysis was done if the extracted data could be merged. MATERIALS AND METHODS We searched MEDLINE, EMBASE, and the Cochrane Central Search library for published studies that analyzed the effect of CRP in RCC. All included cases were categorized into 4 groups of different stages and tumor types for analysis, and the relationships between CRP and stage, grade, and survival were analyzed. RESULTS Overall, 24 studies including 4,100 RCC cases were accepted for meta-analysis. Elevated CRP level was associated with higher stage (risk ratio [RR] 2.90, 95% confidence interval [CI] 2.52-3.32, P<0.00001) and higher grade (RR 4.31, 95% CI 3.35-5.56, P<0.00001) in the overall analysis of patients with all pathologic types of RCCs, and it was also associated with poorer overall survival (hazard ratio [HR] 1.51, 95% CI 1.09-1.93, P<0.00001) and cancer-specific survival (CSS) (HR 3.91, 95% CI 2.18-5.64, P<0.00001). In patients with localized RCC, elevated CRP level was associated with poorer CSS (HR 3.49, 95% CI 2.93-4.05, P<0.00001) and progression-free survival (HR 3.29, 95% CI 2.91-3.67, P<0.00001); whereas in patients with metastatic RCC, elevated CRP level was associated with poorer overall survival (HR 2.37, 95% CI 2.14-2.60, P<0.00001) and CSS (HR 3.70, 95% CI 3.19-4.22, P<0.00001). Specifically, in the patients with clear cell RCC, elevated CRP level was also associated with higher stage (RR 2.92, 95% CI 2.25-3.80, P<0.00001), poorer CSS (HR 2.60, 95% CI 2.32-2.88, P<0.00001), and poorer progression-free survival (HR 1.21, 95% CI 0.94-1.47, P<0.00001). CONCLUSION Elevated CRP level in a patient with RCC is associated with poorer prognosis, and it could serve as a useful biomarker for clinical prediction.

Periostin Mediates TGF-β-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells

Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.

Periostin: a promising target of therapeutical intervention for prostate cancer

BackgroundIn our recent study, Periostin was up-regulated in prostate cancer(PCa) compared with benign prostate hyperplasia (BPH) by proteomics analysis of prostate biopsies. We investigated the effect of sliencing Periostin by RNA interference (RNAi) on the proliferation and migration of PCa LNCap cell line.MethodsAll the prostate biopsies from PCa, BPH and BPH with local prostatic intraepithelial neoplasm(PIN) were analyzed by iTRAQ(Isobaric tags for relative and absolute quantification) technology. Western blotting and immunohistochemical staining were used to verify Periostin expression in the tissues of PCa. Periostin expression in different PCa cell lines was determined by immunofluorescence staining, western blotting and reverse transcription PCR(RT-PCR). The LNCap cells with Periostin expression were used for transfecting shRNA-Periostin lentiviral particles. The efficancy of transfecting shRNA lentiviral particles was evaluated by immunofluorescence, western blotting and Real-time PCR. The effect of silencing Periostin expression by RNAi on proliferation of LNCap cells was determined by MTT assay and tumor xenografts. The tissue slices from theses xenografts were analyzed by hematoxylin and eosin(HE) staining. The expression of Periostin in the xenografts was deteminned by Immunohistochemical staining and western blotting. The migration of LNCap cells after silencing Periostin gene expression were analyzed in vitro.ResultsPeriostin as the protein of interest was shown 9.12 fold up-regulation in PCa compared with BPH. The overexpression of Periostin in the stroma of PCa was confirmed by western blotting and immunohistochemical staining. Periostin was only expressed in PCa LNCap cell line. Our results indicated that the transfection ratio was more than 90%. As was expected, both the protein level and mRNA level of Periostin in the stably expressing shRNA-Periostin LNCap cells were significantly reduced. The stably expressing shRNA-Periostin LNCap cells growed slowly in vitro and in vivo. The tissues of xenografts as PCa were verificated by HE staining. Additionally, the weak positive Periostin expressed tumor cells could be seen in the tissues of 6 xenografts from the group of down-regulated Periostin LNCap cells which had a significant decrease of the amount of Periostin compared to the other two group. Furthermore, our results demonstrated that sliencing Periostin could inhibit migration of LNCap cells in vitro.ConclusionsOur data indicates that Periostin as an up-regulated protein in PCa may be a promising target of therapeutical intervention for PCa in future.

The 1973 WHO Classification Is More Suitable than the 2004 WHO Classification for Predicting Prognosis in Non-Muscle-Invasive Bladder Cancer

Background Predicting the recurrence and progression of Non-muscle-invasive bladder cancer(NMIBC) is critical for urologist. Histological grade provides significant prognostic information, especially for prediction of progression. Currently, the 1973 and the 2004 WHO classification co-exist. Which system is better for predicting rumor recurrence and progression still a matter for debate. Methodology/Principal Findings 348 patients diagnosed with Non-muscle invasive bladder cancer were enrolled in our retrospective study. Paraffin sections were assessed by an experienced urological pathologist according to both the 1973 and 2004 WHO classifications. Tumor recurrence and progression was followed-up in all patients. During follow-up, corresponding 5-year recurrence-free survival rates of G1, G2 and G3 were 82.1%, 55.9%, 32.1% and the 5-year progression-free survival rates were 95.9%, 84.4% and 43.3%, respectively. The 5-year recurrence-free survival rates of papillary urothelial neoplasm of low malignant potential (PUNLMP), low-grade papillary urothelial carcinoma(LGPUC) and high-grade papillary urothelial carcinoma (HGPUC) were 69.8%, 67.1% and 42.0% respectively and the 5-year progression-free survival rates were 100%, 90.9% and 54.8% respectively. In multivariate analysis, the 1973 WHO classification significantly associated with both tumor recurrence and progression(p = 0.010 and p = 0.022, respectively); the 2004 WHO classification correlated with tumor progression(p = 0.019), while was not proved to be a variable that can predict the risk of recurrence(p = 0.547). Kaplan-Meier plots showed that both the 1973 WHO and the 2004 WHO classifications were significantly associated with progression-free survival (p<0.0001, log-rank test). For prediction of recurrence, significant differences were observed between the tumor grades classified using the 1973 WHO grading system (p<0.0001, log-rank test), while a significant overlap was observed between PUNLMP and LG plots using the 2004 WHO grading system(p = 0.616, log-rank test). Conclusion/Significance Both the 1973 WHO and the 2004 WHO Classifications are effective in predicting tumor progression in Non-muscle invasive bladder cancer, while the 1973 WHO Classification is more suitable for predicting tumor recurrence.

Periostin Mediates TGF-beta-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells.

Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.

A Systematic Review and Meta-Analysis of Current Evidence Comparing Laparoendoscopic Single-Site Adrenalectomy and Conventional Laparoscopic Adrenalectomy

PURPOSE To assess the efficacy and safety of laparoendoscopic single-site adrenalectomy (LESS-A) and conventional laparoscopic adrenalectomy (LA) as a systematic review and meta-analysis of current evidence. METHODS We conducted a thorough search for comparative studies that compared LESS-A and conventional LA in the following databases: MEDLINE, EMBASE, and the Cochrane library. Studies were reviewed independently and rated by Newcastle-Ottawa Quality Assessment Scale. The operative time, estimated blood loss in operation, the time to resume oral intake after surgery, postoperative hospital stay, and the visual analog pain scale (VAPS) score were included for analysis to compare the efficacy, while the complications together with the analgesia use were included for analysis to compare the safety. RESULTS Nine studies with 171 LESS-A cases and 272 conventional LA cases were identified. Although operative time was longer in LESS-A (mean difference [MD] 15.46, 95% confidence interval [CI] 11.18 to 19.74), estimated blood loss (MD 4.72, 95% CI 12.08 to 21.52) and the time to resume oral intake (MD -0.04, 95% CI -0.19 to 0.11) were similar; LESS-A presented a shorter postoperative stay in hospital (MD -0.60, 95% CI -0.86 to -0.35) and lower VAPS score (MD -1.21, 95% CI -1.44 to -0.97). Besides, the risk of minor postoperative complications (risk ratio [RR] 1.74, 95% CI 0.78 to 3.87) was similar. The postoperative analgesia demand in total (RR 0.65, 95% CI 0.52 to 0.81) together with the analgesia usage lasting more than 24 hours after surgery (RR 0.35, 95% CI 0.21 to 0.58) were associated with lower risk in LESS-A, however. CONCLUSIONS Based on current evidence, the operative time seems to be longer in LESS-A; however, operative blood loss and complications are similar. In addition, LESS-A presents a shorter hospital stay after surgery and more acceptable perception of pain than conventional LA.

Ki-67 is an independent indicator in non–muscle invasive bladder cancer (NMIBC); Combination of EORTC risk scores and Ki-67 expression could improve the risk stratification of NMIBC

OBJECTIVE To prove the predicting role of Ki-67 expression and to demonstrate that the combination of European Organization for Research and Treatment of Cancer (EORTC) risk scores and Ki-67 staining status could improve the risk stratification in a large series of patients with non-muscle invasive bladder cancer (NMIBC). MATERIAL AND METHODS From October 2002 to July 2010, in our cohort, 332 patients who were treated with transurethral resection of the bladder tumor were diagnosed with NMIBC by histopathologic analysis. Two experienced uropathologists rereviewed the slides. The EORTC risk scores for recurrence and progression were determined. Ki-67 expression was evaluated using immunohistochemical studies and scored for intensity and area of staining. We correlated Ki-67 expression scores with clinical and pathologic variables. We evaluated the prognosis role of EORTC risk scores, Ki-67 staining, and their combination on tumor recurrence-free survival and progression-free survival (PFS) by univariate analysis, multivariate analysis, and Kaplan-Meier survival curves. RESULTS With a median follow-up of 47 (range, 2-124) months, 119 patients (35.8%) had tumor recurrence and 40 patients (12%) had tumor progression. Ki-67 positivity (Ki-67>25%) was reported in 108 tumors (32.5%), and it was significantly associated with high EORTC risk scores for both tumor recurrence and progression. In univariate analysis, multifocality, tumor size, tumor stage, tumor grade, and Ki-67 staining correlated with recurrence-free survival, whereas tumor size, tumor stage, tumor grade, concomitant CIS, and Ki-67 staining correlated with PFS. In multivariable analysis, Ki-67 expression was an independent risk factor for predicting tumor recurrence (hazard ratio, 2.14; P<0.0001) and progression (hazard ratio: 2.97, P = 0.004). Kaplan-Meier curves showed that combining EORTC risk scores and Ki-67 staining led to more accurate prediction for tumor recurrence and progression (log-rank test; P<0.0001). CONCLUSIONS Ki-67 positivity is prognostic for predicting tumor recurrence and progression. Combination of EORTC risk scores with Ki-67 expression could improve the risk stratification for both recurrence and progression in NMIBC.

Are EORTC risk tables suitable for Chinese patients with non-muscle-invasive bladder cancer?

OBJECTIVE To evaluate the applicability of using EORTC risk tables in Chinese patients with non-muscle-invasive bladder cancer. MATERIAL AND METHODS Between October 2000 and July 2009, 301 patients with NMIBC who underwent transurethral resection of the bladder tumor (TURBT) at our hospital were followed up. The probability of recurrence and progression at 1 year and 5 years post-operatively was calculated along with the 95% confidence intervals. We then compared the actual probabilities in our center to those obtained through the application of the EORTC risk tables. RESULTS Median patient age was 67 years (range, 21-92 years), and the median follow-up duration was 46 months (range, 2-151 months). The probability of recurrence at 1 year ranged from 2% to 58%, and the probability of progression ranged from less than 1.2% to 30%. At 5 years, the probability of recurrence ranged from 12% to 85%, and the probability of progression ranged from less than 2.9% to 50%. An overlapping of the confidence intervals of the probability between our series and the EORTC group is detected. CONCLUSIONS Although the immediate instillation of intravesical chemotherapy may reduce the risk of recurrence, EORTC risk tables could predict recurrence and progression in Chinese patients with non-muscle-invasive bladder cancer.

Retroperitoneal Laparoscopic Ureterolithotomy for Proximal Ureteral Calculi in Selected Patients

Objectives. To summarize our experience of retroperitoneal laparoscopic ureterolithotomy for ureteral calculi and evaluate the safety and efficiency of this procedure. Methods. We conducted a retrospective analysis of 197 patients with proximal ureteral calculi who accepted retroperitoneal laparoscopic ureterolithotomy from June 2005 to June 2014. Results. All procedures were performed successfully and the mean operating time and estimated blood loss were 87 min and 64 mL. The clearance rate was 98.5% and the rates of urine leak and ureteral stricture were 2.5% and 1.0%. Conclusions. Retroperitoneal laparoscopic ureterolithotomy is a safe and effective procedure for patients with complex stones or anatomic abnormalities, and, with experience of high volume series, it is also a reasonable choice as the primary treatment for such selected patients.