[Show abstract][Hide abstract] ABSTRACT: Background
Aberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients.Methods
In a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3¿144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.ResultsThirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2¿139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P¿=¿0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P¿=¿0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P¿=¿0.039), lack of bladder recurrence prior to contralateral UTUC (P¿=¿0.009), history of renal transplantation (P¿<¿0.001), and preoperative renal insufficiency (P¿=¿0.002) are independent risk factors for contralateral UTUC recurrence after RNU.Conclusions
Our data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.
Journal of experimental & clinical cancer research : CR. 01/2015; 34(1):5.
[Show abstract][Hide abstract] ABSTRACT: Purpose To explore the characteristics, predictive risk factors, and prognostic effect of concomitant non-muscle-invasive bladder cancer (NMIBC) in patients with upper tract urothelial carcinoma (UTUC). Methods We evaluated 727 consecutive UTUC patients treated with radical resection between 2000 and 2012 in a high-volume center of China. Preoperative cystoscopy was performed in all patients. Patients with previous or concomitant total cystectomy were excluded. Results Overall, 73 patients (10.0 %) had NMIBC. Concomitant NMIBC was associated with previous bladder cancer (p = 0.003), tumor located in ureter (p = 0.008), multifocality (p p = 0.023). The presence of concomitant NMIBC was predictive for lower tumor stage (p = 0.019), papillary architecture (p = 0.023), and organ-confined disease (pT p = 0.006). The median follow-up duration was 57 months. The presence of concomitant NMIBC was a risk factor for bladder recurrence (p p = 0.030) and contralateral recurrence (odds ratio, 1.907, p = 0.016). Most concomitant NMIBC were found at the lateral wall or bladder neck, while most intravesical recurrences occurred near the site of surgery or posterior wall. Conclusions The most common site for concomitant NMIBC was lateral wall and bladder neck, and previous bladder cancer, tumor located in ureter, tumor multifocality, and preoperative renal insufficiency were risk factors for concomitant NMIBC. The presence of concomitant NMIBC is predictive for relative better pathologic outcomes but higher rate of bladder recurrence, while the effect on postoperative survival was limited with patients early-stage UTUCs. The potential mechanisms need further investigation.
Annals of Surgical Oncology 01/2015; · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer is a leading cause of cancer-related death among men. Early diagnosis and treatment are successful against prostate cancer, yet the clinical treatment of advanced prostate cancer remains a challenge. Gemcitabine is used to treat a broad spectrum of solid tumors; however, the clinical response of prostate cancer patients to gemcitabine is limited. In the present study, we showed that HMGN5, a nucleosome binding protein that can unfold chromatin by binding to histone (H1), is overexpressed in prostate cancer cells and plays an oncogenic role in prostate cancer tumorigenesis and development by activating the MAPK signaling pathway. We also found that sensitivity of prostate cancer cells to gemcitabine was positively correlated with HMGN5 expression. Knockdown of HMGN5 expression reduced the sensitivity of PC-3 cells to gemcitabine, and ectopic HMGN5 expression in DU145 cells enhanced the sensitivity to gemcitabine. Gemcitabine decreased HMGN5 expression, consequently leading to inactivation of the MAPK signaling pathway and cleavage of the PARP protein. Finally, we showed that PC-3 cells acquire gemcitabine resistance by gradual loss of HMGN5 expression. The present study suggests that HMGN5 is a potential biomarker for treating prostate cancer, and patients with a high level HMGN5 will benefit from gemcitabine treatment.
[Show abstract][Hide abstract] ABSTRACT: Potassium inwardly rectifying channel, subfamily J, member 1 (KCNJ1), as an ATP-dependent potassium channel, plays an essential role in potassium balance. KCNJ1 variation is associated with multiple diseases, such as antenatal Bartter syndrome and diabetes. However, the role of KCNJ1 in clear cell renal cell carcinoma (ccRCC) is still unknown. Here, we studied the expression and function of KCNJ1 in ccRCC. The expression of KCNJ1 was evaluated in ccRCC tissues and cell lines by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry analysis. The relationship between KCNJ1 expression and clinicopathological characteristics was analyzed. p3xFLAG-CMV-14 vector containing KCNJ1 was constructed and used for transfecting ccRCC cell lines 786-O and Caki-2. The effects of KCNJ1 on cell proliferation, invasion, and apoptosis were detected in ccRCC cell lines using cell proliferation assay, transwell assay, and flow cytometry, respectively. We found that KCNJ1 was low-expressed in ccRCC tissues samples and cell lines, and its expression level was significantly associated with tumor pathology grade (P = 0.002) and clinical stage (P = 0.023). Furthermore, the KCNJ1 expression was a prognostic factor of ccRCC patient's survival (P = 0.033). The re-expression of KCNJ1 in 786-O and Caki-2 significantly inhibited cancer cell growth and invasion and promoted cancer cell apoptosis. Moreover, knockdown of KCNJ1 in HK-2 cells promoted cell proliferation. Collectively, these data highlight that KCNJ1, low-expressed in ccRCC and associated with poor prognosis, plays an important role in ccRCC cell growth and metastasis.
[Show abstract][Hide abstract] ABSTRACT: Objectives
To investigate the incidence and treatment strategies for bilateral upper tract urothelial carcinoma (UTUC) and to compare the characteristic and oncologic outcomes of bilateral UTUC with those of unilateral tumors.
Methods and materials
The study included 892 consecutive patients with UTUC. Bilateral UTUC was defined as synchronous bilateral carcinoma on preoperative imaging before confirmation by pathology or positive urine cytology result plus direct visualization. Radical nephroureterectomy (RNU) or nephron-sparing surgery (NSS) or both were carried out.
A total of 39 patients (4.37%) suffered from bilateral disease. Discordant histological grade of bilateral tumor was found in 39.3% cases. Bilateral tumors were associated with female sex (P<0.001), preoperative renal insufficiency (P<0.001), previous or concomitant bladder tumors (P = 0.013), lower tumor stages (P = 0.020), papillary architecture (P = 0.001), and smaller-sized tumors (P = 0.020). Patients with worse renal function (P<0.001) or large-sized tumors (P = 0.039) tended to be treated with bilateral RNU. Most patients (67.6%) were treated with unilateral RNU plus unilateral NSS, with NSS being performed on tumors that only extended to the ureter (P = 0.003) and had a smaller size (P = 0.005). The median follow-up duration was 56 months. The 5-year cancer-specific survival and bladder recurrence-free survival rates were 81.2% and 64.5%, respectively, similar to those of unilateral tumors. Male sex (hazard ratio = 11.535) and higher tumor stage (hazard ratio = 3.386) were independent worse prognostic factors.
The prevalence of bilateral UTUC is rare. Female patients, patients with renal insufficiency, and those with bladder tumor tended to suffer from bilateral disease and were less likely to present with worse pathological outcomes in the Chinese population. The tumor characteristics and renal function were informative in treatment selection. The oncologic outcomes were similar to those in unilateral UTUC, and male sex and a higher tumor stage were poor prognostic factors for these patients.
[Show abstract][Hide abstract] ABSTRACT: MicroRNAs are endogenous small noncoding RNAs that are functionally involved in numerous critical cellular processes including tumorigenesis. Data mining using a microRNA array database suggested that let-7d microRNA may be associated with renal cell carcinoma (RCC) malignant progression. Here, we performed further analyses to determine whether let-7d is functionally linked to RCC malignancy.
Molecular Cancer 09/2014; 13(1):206. · 5.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 61-year-old male patient presented with intermittent gross hematuria. A right renal mass with infrahepatic vena caval tumor thrombus was found using magnetic resonance imaging. We undertook a novel combined retroperitoneal and transperitoneal pure laparoscopic nephrectomy with vena caval thrombectomy for this patient. The patient recovered well after surgery and discharged on day 6. A clear cell renal cell carcinoma with venous extension was confirmed by pathologic assay. To our knowledge, this is the first report of such a novel hybrid surgical strategy.
[Show abstract][Hide abstract] ABSTRACT: The advent of targeted therapy has proved a milestone in the history of metastatic renal cell carcinoma treatment, and several guidelines now recommend sunitinib as first- or second-line treatment. But little is known about its efficacy in Asian patients. The aim of this article was to evaluate the efficacy of sunitinib monotherapy in patients with metastatic renal cell carcinoma treated at two Chinese centers.
One hundred and forty-one patients with metastatic renal cell carcinoma were included in the study. Of them, 119 patients received single-agent sunitinib as first-line therapy and the remaining 22 patients received it as second-line therapy. One hundred and twenty patients received sunitinib in a dosage of 50 mg orally once daily on a 4-2 schedule (4 weeks on treatment, 2 weeks off), while 21 patients received 37.5 mg/day continuously until either disease progression or unacceptable toxicity occurred. The overall response rate, survival outcomes, and safety were evaluated.
Over a median follow-up time of 23 months (16 cycles; range 2-45 months), complete responses, partial responses, and stable disease lasting two cycles or longer were achieved in 2.8%, 24.1%, and 60.3% of patients respectively (objective response rate 26.9%; overall benefit 87.2%). The median progression-free survival was 14.2 months (range 3-39 months). During the study, 53 patients died and the median survival time was 13.5 months (range 7-25 months). Dose modification or treatment interruption due to adverse events was required in 36.9% of the patients. The most common adverse events were hand-foot syndrome (71.4%), thrombocytopenia (68.8%), hypertension (47.1%), and fatigue (46.3%).
Sunitinib had a favorable efficacy/tolerability profile in Chinese patients with metastatic renal cell carcinoma.
Chinese medical journal 04/2014; 127(8):1450-3. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP, which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and apoptosis, including the tumor suppressor PTEN, ERK phosphatases, the proapoptotic molecule Daxx, and the Hedgehog pathway transcription factor Gli2. Knockdown of SPOP specifically kills ccRCC cells, indicating that it may be a promising therapeutic target. Collectively, our results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis.
[Show abstract][Hide abstract] ABSTRACT: To compare the transperitoneal laparoscopic radical prostatectomy procedures with extraperitoneal laparoscopic radical prostatectomy procedures to assess for differences in outcomes and complications.
A retrospective review 190 patients who had received laparoscopic radical prostatectomy for prostate cancer from June 2002 to January 2013. The results were compared between 116 transperitoneal laparoscopic radical prostatectomy procedures and 74 extraperitoneal laparoscopic radical prostatectomy procedures.
The cohorts were similar in terms of mean patient age, height, weight, body mass index, Gleason score from biopsy, and clinical stage. Patients receiced extraperitoneal laparoscopic radical prostatectomy had shorter operation time (146 minutes vs. 224 minutes, Z = -7.220, P = 0.000), less postoperative drainage time (3 days vs. 7 days, Z = -7.115, P = 0.000) and shorter postoperative length of hospital stay (5 days vs. 10 days, Z = -7.250, P = 0.000) than patients receiced transperitoneal procedures. However, the Gleason score, pathological stage, positive margin rate, intraoperative and early postoperative complications has no differences between the 2 groups (P > 0.05).
The patients who received extraperitoneal laparoscopic radical prostatectomy had shorter operative time and revovered faster recovery and the effect of surgery was similar.
Zhonghua wai ke za zhi [Chinese journal of surgery] 02/2014; 52(2):135-8.
[Show abstract][Hide abstract] ABSTRACT: To explore the risk factors and treatment outcomes of contralateral new upper tract urothelial carcinoma (UTUC) after nephroureterectomy in a large single-center cohort of UTUC patients.
A retrospective analysis of the clinicopathological data of 509 consecutive patients treated by nephroureterectomy from 2000 to 2010 at a high-volume center in China was conducted.
Thirty-five patients (6.9 %) were found to develop contralateral UTUC. Gross hematuria was a common symptom, and aristolochic acid (AA) containing Chinese herbs was identified as an underlying cause. In multivariate analysis, renal transplant recipients (HR = 16.507) and preoperative renal insufficiency (HR = 2.523) were independent risk factors. No correlation was found in the clinical and pathological characteristics of primary and subsequent contralateral UTUC. A second round of nephroureterectomy should be performed on renal transplant patients, whereas patients who are older, exhibit relatively better renal function, and have tumors that are single, located in the ureter and small size could be treated with nephron-sparing surgery. No survival difference was detected between the two treatment groups, and developing contralateral UTUC was not associated with worse survival.
Contralateral UTUC is comparatively rare, and gross hematuria is a common symptom. Renal transplant history and renal insufficiency are independent risk factors, and prophylactic contralateral nephroureterectomy is considered for uremic UTUC patients with proper renal replacement treatment or renal transplant recipients. These features are likely related to the mechanisms of multifocality of UTUC, and the potential correlation with AA remains to be elucidated. Tumor characteristics and renal function are informative for the decisions concerning surgical options for contralateral UTUC.
Journal of Cancer Research and Clinical Oncology 01/2014; · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives. To report the decline of renal function after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC) patients and to develop a nomogram to predict ineligibility for cisplatin-based adjuvant chemotherapy (AC). Methods. We retrospectively analyzed 606 consecutive Chinese UTUC patients treated by RNU from 2000 to 2010. We chose an eGFR of 60 and 45 ml/min/1.73 m(2) as cut-offs for full-dose and reduced-dose AC eligibility. Results. Median eGFR for all patients before and after surgery was 64 and 49 ml/min/1.73 m(2) (P < 0.001). The proportion of patients ineligible to receive full-dose and reduced-dose AC changed from 42% to 74% and from 20% to 38.1%. Older age (OR = 1.007), preoperative eGFR (OR = 0.993), absence of hydronephrosis (OR = 0.801), smaller tumor size (OR = 0.962), and tumor without multifocality (OR = 0.876) were predictive for ineligibility for full-dose AC. Preoperative eGFR (OR = 0.991), absence of hydronephrosis (OR = 0.881), tumor located in renal pelvis (OR = 1.164), and smaller tumor size (OR = 0.969) could predict ineligibility for reduced-dose AC. The c-index of the two models was 0.757 and 0.836. Postoperative renal function was not associated with worse survival. Conclusions. Older age, lower preoperative eGFR, smaller tumor size, tumor located in renal pelvis, and absence of hydronephrosis or multifocality were predictors of postoperative renal insufficiency.
BioMed Research International 01/2014; 2014:529186. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Kaempferol (Kae), a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to be associated with phosphatase and the tensin homolog deleted on the chromosome 10 (PTEN)/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown cells. Our findings indicate that Kae could be an alternative medicine for bladder cancer, based on a PTEN activation mechanism.
International Journal of Molecular Sciences 11/2013; 14(11):21215-21226. · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate variation in the International Prostate Symptom Score (IPSS) in men following prostate brachytherapy.
From January 2004 to November 2009, 524 consecutive patients underwent prostate brachytherapy either alone or in combination with external beam radiation therapy for T1c-T3b prostate cancer. The IPSS was assessed preimplant and at 1, 6, 12, 24, 36, and 48 months after treatment. Clinical and treatment-related factors were assessed for correlations with the IPSS increase.
The mean preimplant IPSS was 7.4, with the greatest mean score of 16.0 at 1 month. At 6 months, the mean total IPSS had decreased to 11.5, but it was still statistically significantly greater than that at baseline (<0.001). At 12 months, the IPSS was decreased to 8.6, slightly greater than baseline (p = 0.001). The IPSS of 45.4 % (69/152) patients gradually returned to preimplant levels and that of 71.1 % (108/152) patients returned to within 3 points of the baseline at 24 months. At 24, 36, and 48 months after seed implantation, the IPSS was 8.6, 7.7, and 8.2, respectively, and none of these values differed statistically significantly from baseline (p > 0.05). Sixteen patients (3.1 %) showed AUR, and 11 patients required catheterization. On univariate and multivariate analyses, the IPSS increase was best predicted by lower preimplant IPSS.
In our series, IPSS after prostate brachytherapy peaked at 1 month and gradually returned to approximately baseline at 24 months. The IPSS increase was best predicted by lower preimplant IPSS.
World Journal of Urology 10/2013; 32(4). · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To describe a novel technique using extracorporeal tailoring and an inverted ureteral nipple to perform laparoscopic transperitoneal ureteral reimplantation for adult obstructed megaureter and our initial experience with 10 patients.
Ten patients (mean age 39.2 years [range, 21-62]) with adult obstructed megaureter underwent transperitoneal laparoscopic ureteral reimplantation by a 3- or 4-port technique. In each case, the affected ureter was freed and delivered out of the peritoneal cavity through the ipsilateral 12-mm port. The lower end of the ureter was tailored by approximately 6 cm, and the tip was folded back onto itself and secured with absorbable sutures to form a nipple. A double-J stent was placed, the entire assembly was carefully replaced into the abdomen, and the ureter was reimplanted into the posterolateral wall of the bladder.
Surgery was successful in all the 10 patients without the need for open conversion. At a mean follow-up of 17 months, all patients were asymptomatic, and hydronephrosis was relieved in 9 cases. Laparoscopic ureteral reimplantation with extracorporeal tailoring and direct nipple ureteroneocystostomy is an easy, safe, and effective procedure for adult obstructed megaureter.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND/PURPOSE: There is relatively little literature on prevalence of chronic kidney disease (CKD) prior to surgery in patients with upper urinary tract urothelial carcinoma (UTUC). We evaluated the prevalence and clinical associated factors of baseline CKD in patients with UTUC. MATERIALS AND METHODS: There were 785 patients with a pathologic diagnosis of UTUC from January 2002 to December 2011 who were analyzed in this study. Estimated glomerular filtration rate (eGFR) was calculated by re-expressed Modification of Diet in Renal Disease (MDRD) formulas for the Chinese population. A multivariate logistic regression was performed to evaluate the odds ratios (ORs) for CKD stage 3 or higher in UTUCs after data differences were tested. RESULTS: The prevalence of CKD in UTUCs presenting at our hospital was 58.6% and 70.8% in the group age 70 years and older. Older age [per year increased; OR = 1.050; 95% confidence interval (CI): 1.034-1.067], lower tumor stage (T stage; per stage increased; OR = 0.666; 95% CI: 0.544-0.816), higher tumor grade (per grade increased; OR = 1.392; 95% CI: 1.004-1.930) and the main tumor locating in the pelvis (ureter as reference; OR = 0.648; 95% CI: 0.475-0.885) were independently associated with decreased kidney function in the multivariate logistic regression. The use of serum creatinine (Scr) only to evaluate the renal function would ignore a large proportion of patients suffering from CKD stage 3 in UTUCs, especially in those older than 70 years (39.3% vs. 54.1%, p = 0.022). CONCLUSION: We demonstrated a high prevalence (58.6%) of CKD in patients with UTUC, particularly in the group older than 70 years (70.8%). Older age, lower T stage, higher tumor grade, and the main tumor locating in pelvis (ureter as reference) were independently associated with CKD in UTUCs.
Journal of the Formosan Medical Association 05/2013; · 1.70 Impact Factor