Wenlian Xie

Laparoscopic Radical Cystectomy with Orthotopic Ileal Neobladder for Bladder Cancer: Oncologic Results of 171 Cases With a Median 3-Year Follow-up

BACKGROUND Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard treatment for muscle-invasive and high-risk non-muscle-invasive bladder cancer (BCa). Large series with long-term oncologic data after laparoscopic RC (LRC) are rare. OBJECTIVE To report oncologic outcomes of LRC for 171 cases with a median 3-yr follow-up. DESIGN, SETTING, AND PARTICIPANTS From December 2002 to June 2009, 171 consecutive patients with BCa who underwent LRC with orthotopic ileal neobladder (OIN) at our institution were enrolled in this retrospective study. INTERVENTION All patients underwent LRC OIN. Adjuvant chemotherapy was administered to patients with non-organ-confined disease or positive lymph nodes. MEASUREMENTS The demographic, perioperative, complication, pathologic, and survival data were collected and analysed. RESULTS AND LIMITATIONS Most tumours were transitional cell carcinoma (TCC; 160, 93.6%). Tumours were organ confined in 113 patients (pT1-T2; 66.1%) and non-organ confined in 58 patients (pT3-T4a; 33.9%). There was involvement of the lymph nodes in 38 patients (22.2%). Surgical margins were all tumour free. The mean number of removed lymph nodes was 16 (5-46). Follow-up ranged from 3 to 83 mo, and 54 (31.6%) patients completed 5-yr follow-up. Two patients (1.2%) had local recurrence and distant metastasis, 9 patients (5.3%) had local recurrence alone, and 23 patients (13.5%) had distant metastasis. One patient (0.6%) had port-site seeding. One hundred twenty-four patients (72.5%) were alive with no evidence of recurrence; 28 patients (16.4%) died, 20 from metastasis and 8 from tumour-unrelated causes. The estimated 5-yr overall survival, cancer-specific survival, and recurrence-free survival rates were 73.7%, 81.3%, and 72.6%, respectively. The relatively low percentage of patients reaching 5-yr follow-up is a limitation of this retrospective study. CONCLUSIONS Surgical technique of LRC with OIN can achieve the established oncologic criteria of open surgery, and our oncologic outcome is encouraging. Long-term follow-up is needed for further confirmation.

Laparoscopic Radical Cystectomy with Orthotopic Ileal Neobladder: A Report of 85 Cases

PURPOSE The preliminary results of laparoscopic radical cystectomy in 85 patients are presented in this study. The functional and oncologic outcomes of this procedure in these patients are discussed. PATIENTS AND METHODS Between December 2002 and May 2006, we performed 85 laparoscopic radical cystectomies with orthotopic ileal neobladder for bladder cancer in 77 men and 8 women. A 5-port transperitoneal approach was applied. The standard bilateral pelvic lymphadenectomy was performed first, then radical cystectomy was completed laparoscopically. The construction of the ileal neobladder and the anastomosis of ureter-neobladder were performed extracorporeally. The neobladder was anastomosed to the urethral stump under laparoscopy. A nerve-sparing procedure was performed for eight patients. RESULTS The median operative time was 320 min, and the median blood loss was 280 mL. Conversion to open surgery was not necessary in any of the patients. The average time to oral intake after operation was 3.9 days. There were no perioperative mortalities. The complication rate was 14.1% (12/85), including such complications as three uretero-pouch anastomotic strictures, one vesicourethral anastomotic stricture, one pouch-vaginal fistula, one colonic pouch fistula, one ileo-pouch fistula, three ileus, one pneumonia, and one pyelonephritis. The daytime continence rate was 91.2%, and the nighttime continence rate was 82.4% at 6 months postoperatively. The neobladder capacity was about 343 mL. Surgical margins were tumor free for all patients. Of the eight patients who underwent a nerve-sparing procedure, four patients had potency for intercourse. During a follow-up period of 1 to 41 months (average 21.3 months), three patients had local recurrence, one patient had trocar site seeding, and five patients had distant metastasis, of whom four died. CONCLUSIONS Laparoscopic radical cystectomy with extracorporeal formation of a neobladder is a feasible procedure with low morbidity and acceptable neobladder function. Long-term follow-up is needed to confirm the oncologic outcomes.

A prospective randomised controlled trial of laparoscopic vs open radical cystectomy for bladder cancer: perioperative and oncologic outcomes with 5-year follow-upT Lin et al.

Background:Laparoscopic radical cystectomy (LRC) is increasingly being used for muscle-invasive bladder cancer. However, high levels of clinical evidence comparing laparoscopic vs open radical cystectomy (ORC) are lacking.Methods:A prospective randomised controlled clinical trial comparing LRC vs ORC in patients undergoing radical cystectomy for bladder cancer. Thirty-five patients were eligible for final analysis in each group.Results:The median follow-up was 26 months (range, 4–59 months) for laparoscopic vs 32 months (range, 6–60 months) for ORC. Significant differences were noted in operative time, estimated blood loss (EBL), blood transfusion rate, analgesic requirement, and time to resumption of oral intake. No significant differences were noted in the length of hospital stay, complication rate, lymph node yield (14.1±6.3 for LRC and 15.2±5.9 for ORC), positive surgical margin rate, postoperative pathology, or recurrence rate (7 for LRC and 8 for ORC). The 5-year recurrence-free survival with laparoscopic vs ORC was 78.5% vs 70.9%, respectively (P=0.773). The overall survival with laparoscopic vs ORC was 73.8% vs 67.4%, respectively (P=0.511).Conclusion:Our study demonstrated that LRC is superior to ORC in perioperative outcomes, including EBL, blood transfusion rate, and analgesic requirement. We found no major difference in oncologic outcomes. The number of patients is too small to allow for a final conclusion.

Hybrid Laparoscopic Endoscopic Single-Site Surgery for Radical Cystoprostatectomy and Orthotopic Ileal Neobladder: An Initial Experience of 12 Cases

BACKGROUND AND PURPOSE Laparoscopic endoscopic single-site surgery (LESS) has recently emerged as an attempt to enhance cosmetic benefits and reduce morbidity; however, LESS for radical cystectomy is still not well established. Here we describe the technique of hybrid LESS for radical cystoprostatectomy and orthotopic ileal neobladder (RC-OIN), and evaluate its feasibility and safety. PATIENTS AND METHODS Between November 2008 and October 2009, 12 men with bladder cancer underwent hybrid LESS for RC-OIN. A homemade multichannel port, made from two stretchable rings and a surgical glove with trocars and valves attached to its fingers, was placed into a 4- to 5-cm midline incision in the lower abdomen and was used for laparoscopic instruments. Another subumbilical port was placed for the laparoscope. Extended bilateral pelvic lymphadenectomy was performed by the lateral view; radical cystoprostatectomy was completed laparoscopically; construction of the ileal neobladder was performed extracorporeally; and the neobladder was anastomosed to the urethral stump laparoscopically, with a slipknot running suture technique. Perioperative, functional, oncologic data and complications were collected and analyzed. RESULTS All operations were performed successfully without conversion to conventional laparoscopic radical cystectomy or open surgery. There was no perioperative mortality or port-related complications. The median operative time was 383 minutes. Median blood loss was 150 mL. A median of 25 lymph nodes were removed. Surgical margins were tumor free in all cases. CONCLUSIONS Hybrid LESS for RC-OIN is technically feasible with effects similar to those of conventional laparoscopic procedures. Further instrument and technique improvement are necessary to shorten operative time and reduce intraoperative difficulties.

Knockdown of Bmi1 inhibits the stemness properties and tumorigenicity of human bladder cancer stem cell-like side population cells

B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) is directly involved in cell growth, proliferation and self-renewal of cancer stem cells (CSCs). The aim of the present study was to assess the role of Bmi1 in the maintenance of stemness properties and tumorigenicity of human bladder CSC-like side population (SP) cells. SP cells were sorted by flow cytometry using Hoechst 33342 staining. Bmi1 mRNA and protein expression in SP and non-SP (NSP) cells was analyzed by quantitative PCR, immunofluorescence and western blotting. The stemness properties of SP cells included cell proliferation, migration, self-renewal, chemotherapy resistance and cell cycle progression were assessed. Tumor formation was also assessed in human bladder cancer xenografts after Bmi1 silencing. The mRNA expression of Bmi1 was upregulated in SP cells when compared with that in the NSP cells. Knockdown of Bmi1 in SP cells resulted in inhibition of cell proliferation, migration and tumor sphere formation, enhanced sensitivity to cisplatin, and cell cycle arrest in the G0/G1 phase. Bmi1 knockdown inhibited cell cycle progression through derepression of the p16INK4a/p14ARF locus. Bmi1-siRNA SP cells failed to produce tumors in recipient mice, while typical urothelial carcinoma formed from subcutaneously injected scramble-siRNA SP cells. Bmi1 is crucial for the maintenance of stemness properties and tumorigenicity of human bladder CSC-like cells. Bmi1 may be a potential therapeutic target for the eradication of CSCs in bladder cancer.

Upregulated GAPLINC predicts a poor prognosis in bladder cancer patients and promotes tumor proliferation and invasion

Previous studies have demonstrated that long noncoding RNAs (lncRNAs) exhibit critical regulatory roles in cancer biology. However, few lncRNAs have been well characterized in bladder cancer. In the previous study, we demonstrated that gastric adenocarcinoma associated, positive CD44 regulator, long intergenic noncoding RNA (GAPLINC) was significantly upregulated in bladder cancer tissues compared with normal tissues in The Cancer Genome Atlas (TCGA) cohort (P=0.039) and a validated cohort of 80 patients with bladder cancer (P=0.021). Statistical analysis revealed that GAPLINC expression level was associated with tumor stage in the validated cohort (P=0.017). Kaplan-Meier analysis demonstrated that patients in the high GAPLINC expression group had a worse overall survival (P=0.0386), indicating that GAPLINC may be a sensitive prognostic biomarker for patients with bladder cancer. Furthermore, knockdown of GAPLINC inhibited cell proliferation and colony formation, promoted cells cycle arrest at G1 phase and suppressed cells migration and invasion. The findings of the present study suggest that GAPLINC exhibits an oncogenic role in bladder cancer and may be a potential prognostic biomarker and therapeutic target.

Knockdown of long non-coding RNA PVT1 induces apoptosis and cell cycle arrest in clear cell renal cell carcinoma through the epidermal growth factor receptor pathway

Previous years have witnessed the importance of long non-coding RNAs (lncRNAs) in cancer research. The lncRNA Pvt1 oncogene (non-protein coding) (PVT1) was revealed to be upregulated in various cancer types. The aim of the present study was to investigate the function of PVT1 in clear cell renal cell carcinoma (ccRCC). The expression of PVT1 in ccRCC was analyzed using reverse transcription-quantitative polymerase chain reaction, and it was revealed that PVT1 expression was upregulated in ccRCC tissues compared with that in normal adjacent tissues. Next, PVT1 expression from The Cancer Genome Atlas datasets was validated, and it was also revealed that the high expression of PVT1 was associated with advanced disease stage and a poor prognosis. Furthermore, the knockdown of PVT1 induced apoptosis by increasing the expression of poly ADP ribose polymerase and Bcl-2-associated X protein, and promoted cell cycle arrest at the G1 phase by decreasing the expression of cyclin D1. Study of the mechanism involved indicated that PVT1 promoted the progression of ccRCC partly through activation of the epidermal growth factor receptor pathway. Altogether, the results of the present study suggested that PVT1 serves oncogenic functions and may be a biomarker and therapeutic target in ccRCC.

Long Non-Coding RNA LUCAT1 Promotes Proliferation and Invasion in Clear Cell Renal Cell Carcinoma Through AKT/GSK-3β Signaling Pathway

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as new regulators and biomarkers in several cancers. However, few lncRNAs have been well characterized in clear cell renal cell carcinoma (ccRCC). Methods: We investigated the lncRNA expression profile by microarray analysis in 5 corresponding ccRCC tissues and adjacent normal tissues. Lung cancer–associated transcript 1 (LUCAT1) expression was examined in 90 paired ccRCC tissues by real-time PCR and validated by The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis was used to examine the prognostic value of LUCAT1 and CXCL2 in ccRCC patients. Loss and gain of function were performed to explore the effect of LUCAT1 on proliferation and invasion in ccRCC cells. Western blotting was performed to evaluate the underlying mechanisms of LUCAT1 in ccRCC progression. Chemokine stimulation assay was performed to investigate possible mechanisms controlling LUCAT1 expression in ccRCC cells. Enzyme-linked immunosorbent assays were performed to determine serum CXCL2 in ccRCC patients and healthy volunteers. Receiver operating characteristic curve analysis was performed to examine the clinical diagnostic value of serum CXCL2 in ccRCC. Results: We found that LUCAT1 was significantly upregulated in both clinical ccRCC tissues (n = 90) and TCGA ccRCC tissues (n = 448) compared with normal tissues. Statistical analysis revealed that the LUCAT1 expression level positively correlated with tumor T stage (P < 0.01), M stage (P < 0.01), and TNM stage (P < 0.01). Overall survival and disease-free survival time were significantly shorter in the high-LUCAT1-expression group than in the low-LUCAT1-expression group (log-rank P < 0.01). LUCAT1 knockdown inhibited ccRCC cell proliferation and colony formation, induced cell cycle arrest at G1 phase, and inhibited cell migration and invasion. Overexpression of LUCAT1 promoted proliferation, migration, and invasion of ccRCC cells. Mechanistic investigations showed that LUCAT1 induced cell cycle G1 arrest by regulating the expression of cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma transcriptional corepressor 1. Moreover, LUCAT1 promoted proliferation and invasion in ccRCC cells partly through inducing the phosphorylation of AKT and suppressing the phosphorylation of GSK-3β. We also revealed that chemokine CXCL2, upregulated in ccRCC, induced LUCAT1 expression and might be a diagnostic and prognostic biomarker in ccRCC. Conclusions: LUCAT1 was upregulated in ccRCC tissues and renal cancer cell lines, and significantly correlated with malignant stage and poor prognosis in ccRCC. LUCAT1 promoted proliferation and invasion in ccRCC cells through the AKT/GSK-3β signaling pathway. We also revealed that LUCAT1 overexpression was induced by chemokine CXCL2. These findings indicate that the CXCL2/LUCAT1/AKT/GSK-3β axis is a potential therapeutic target and molecular biomarker for ccRCC.