MicroRNA-138 Regulates Metastatic Potential of Bladder Cancer Through ZEB2.

BACKGROUND/AIMS: The cases of bladder cancer (BC) with poor prognosis largely result from the distal metastases of the primary tumor. Since microRNAs (miRNAs) play critical roles during cancer metastases, determination of the involved miRNAs in the regulation of the metastases of BC may provide novel therapeutic targets for BC treatment. Here, we aimed to study the role of miR-138 in regulation of BC cell invasion and metastases. METHODS: We analyzed the levels of miR-138 and ZEB2, a key factor that regulates cancer cell invasion, in the BC specimens from the patients. We also studied the correlation between miR-138 and ZEB2. We performed bioinformatics analyses on the binding of miR-138 to the 3'-UTR of ZEB2 mRNA, and verified the biological effects of this binding through promoter luciferase reporter assay. The effects of miR-138-modification on BC cell invasion were evaluated in a transwell cell invasion assay and a scratch would healing assay. RESULTS: We found that the levels of miR-138 were significantly decreased and the levels of ZEB2 were significantly increased in BC specimens, compared to the paired normal bladder tissue. Metastatic BC appeared to contained lower levels of miR-138. Moreover, miR-138 and ZEB2 inversely correlated in BC specimens. Bioinformatics analyses showed that miR-138 targeted the 3'-UTR of ZEB2 mRNA to inhibit its translation. Furthermore, miR-138 overexpression inhibited ZEB2-mediated cell invasion and metastases, while miR-138 depletion increased ZEB2-mediated cell invasion and metastases in BC cells. CONCLUSION: Suppression of miR-138 in BC cells may promote ZEB2-mediated cancer invasion and metastases. Thus, miR-138 appears to be an intriguing therapeutic target to prevent metastases of BC.

[Laparoscopic partial nephrectomy for small renal tumors: report of 59 cases].

OBJECTIVE: To report our initial experiences of laparoscopic partial nephrectomy (LPN) for small renal tumors. METHODS: From July 2005 to December 2008, 59 patients with small renal tumors were resected by laparoscopic partial nephrectomy. RESULTS: All operations were successfully accomplished. Twenty-seven patients were treated via a transperitoneal approach and the other 32 cases a retroperitoneal approach. The average operative duration was 72 minutes (range: 60 -) and the average kidney ischemia time 19 minutes (range: 15 - 32). The estimated blood loss was from 20 - 50 ml and no patient needed transfusion. The collecting system closure was performed by suture in 2 patients, and no complication of hemorrhage or urine leak was found. Thirteen cases used Hemo-lok to clamp the suture instead of traditional ligature. And the mean time of renal warm ischemia was 13 minutes (range: 10 - 18). These patients included 55 with clear cell renal carcinoma, 3 with granule cell renal carcinoma and 1 with oxyphil cell renal carcinoma. All renal tumors were completely removed with a negative surgical margin. The mean postoperative hospital stay was 6.2 days (range: 5 - 10). The postoperative ECT and creatinine were normal and there was no significant difference as compared with the preoperative findings (P < 0.05). None patient had any local recurrence during a mean follow-up period of 24.6 months (range: 3 - 42). CONCLUSIONS: LPN for pT(1) stage renal tumor is both safe and feasible. Mastering the skilled laparoscopic techniques may facilitate operation. Employing Hemo-lok instead of traditional ligature to clamp the suture while sewing renal wound shortens the warm ischemia time.

Laparoscopic radical cystectomy with extracorporeal ileal conduit urinary diversion for treatment of Chinese bladder cancer patients.

PURPOSE: To present our experience in laparoscopic radical cystectomy with extracorporeal urinary diversion for treatment of Chinese bladder cancer patients. METHODS: Between January 2003 and November 2005, 41 men and 5 women with organ-confined muscle-invasive transitional cell carcinoma of the bladder underwent laparoscopic radical cystectomy with the Bricker-type urinary diversion. The age range was 36-71 years. Laparoscopic radical cystectomy and bilateral pelvic lymphadenectomy were performed using five fan-shaped ports by a transperitoneal approach. An ileal conduit diversion was created through the site of specimen retrieval which was the second port at the region of the right pararectus. RESULTS: 46 radical cystectomies with Bricker-type ileal conduits were performed. No conversion to open surgery was necessary. Mean operating time was 220 min (range 120-249 min) for laparoscopic radical cystectomy and 75 min (range 65-120 min) for creating the ileal conduits. Mean estimated blood loss was 276 ml (range 155-567 ml). Two of the 46 patients needed blood transfusion (400 ml each). Mean days to ambulation and oral intake was 4.1 (range 3-5 days) and 3.5 (range 3-6 days), respectively. Mean hospital stay was 17.6 days (range 12-35 days). Mean follow-up was 6.1 months (range 3-19 months). Histopathological examination of the specimens revealed stage T2N0M0 in 18 cases, T3aN0M0 in 14, T3bN0M0 in 9 and T3bN1M0 in 5 (TNM staging). WHO grading: G1 in 2 cases, G2 in 26 cases and G3 in 18 cases. Pelvic metastases appeared in one case and 44 patients are alive and free of disease. Intravenous pyelogram at 3 weeks postoperatively shows no evidence of upper urinary obstruction in 45 patients. CONCLUSION: Despite technical difficulties, laparoscopic radical cystectomy with Bricker-type urinary diversion is feasible. With more experience in the surgical technique, laparoscopic radical cystectomy with extracorporeal urinary diversion can become an alternative treatment of choice in the selected patients with organ- confined bladder cancer in China.

[Laparoscopically ureteroplasty in treatment of congenital obstructive megaureter in childhood: report of 3 cases].

OBJECTIVE: To explore the technique and efficacy of laparoscopic ureteroplasty in treatment of congenital obstructive megaureter in childhood. METHODS: Three children with congenital obstructive megaureter, all male, aged 7 approximately 24, underwent laparoscopic surgery. The dilated ureter was dissected and cut off near the place connecting the ureter and the bladder by laparoscopy. A double J tube was placed in the free ureter and connected with the urinary catheter by 7 - 0 wire. Then the free ureter was sutured with the bladder mucosa by laparoscopy. RESULTS: The operation duration was 80 to 200 min and blood loss was 30 to 50 ml. No complication developed. The double J was removed 10 days after the operation. Follow-up for 4 approximately 24 months showed good ureter drainage in all 3 cases without any infection, obstruction and hydrops. CONCLUSION: Laparoscopic surgery to treat megaureter in childhood has the benefits of slight injury and fast recovery in a short-time follow-up.

ANTITUMOR EFFECTS OF CHRYSANTHEMIN IN PC-3 HUMAN PROSTATE CANCER CELLS ARE MEDIATED VIA APOPTOSIS INDUCTION, CASPASE SIGNALLING PATHWAY AND LOSS OF MITOCHONDRIAL MEMBRANE POTENTIAL.

BACKGROUND: The main objective of the current research work was to investigate the antitumor and apoptotic effects of chrysanthemin in PC-3 human prostate cancer cells. MATERIALS AND METHODS: MTT assay was used to evaluate the effects of chrysanthemin on cell viability whereas flow cytometry along with fluorescence microscopy were used to study apoptotic induction in these cells. Effects on caspase activation were detected through western blot assay. RESULTS: Results showed that chrysanthemin inhibited cancer cell growth in PC-3 cancer cells in a time-dependent as well as concentration-dependent manner. Chrysanthemin-treated cells at 10, 50 and 150 µM doses led to 34.2%, 56.7% and 69.1% apoptosis in these cells respectively. The percentage of cells with depolarized mitochondria increased from 5.3% in untreated control cells to 27.2%, 57.6% and 86.9% in cells treated with 10, 50 and 150 µM dose of chrysanthemin respectively. Chrysanthemin also enhanced the activity of all three caspases viz., caspase-3, 8 and 9 in a dose-dependent fashion. CONCLUSIONS: The study concluded that chrysanthemin ledanticancer effects in PC-3 prostate cancer cells by inducing apoptosis, activating caspasesignaling pathway and loss of mitochondrial membrane potential.

Combination of laparoscopic and open procedure in dismembered pyeloplasty: report of 51 cases.

BACKGROUND: Laparoscopic dismembered pyeloplasty with less trauma than open surgery is commonly performed for ureteropelvic junction obstruction despite a longer operating time and a long learning curve. We describe in this paper a new technique, which combines laparoscopic and open procedure in dismembered pyeloplasty, that we have developed in 51 patients and achieved excellent results. METHODS: The surgical procedure can be divided into two steps: laparoscopic dissection of the renal pelvis and proximal ureter transperitoneally; then accomplishing the pyeloplasty through the extended port incision above the ureteropelvic junction as in open surgery. RESULTS: All 51 operations were successful without conversion to open surgery. No intraoperative complications were observed. The operating time was 40 minutes to 90 minutes with an average of 57.5 minutes. The estimated blood loss was 15 ml to 30 ml with an average of 21.2 ml. Aberrant artery vessel and primary stricture as the cause of ureteropelvic junction obstruction was noted in 2 and 49 patients, respectively. Thirty-nine patients had fever to differing extents in the 4 days postoperation and no severe infection was observed. Four patients had urinary leakage with their drains being retained for 6 days, 6 days, 5 days or 8 days after the operation. The mean followup was 10.8 months (range 3 months to 36 months). The followup showed good results with symptom resolution in all the patients. Renal ultrasonography demonstrated that the average separation of the collecting systems decreased from preoperative 2.7 cm (range 2.0 cm to 4.7 cm) to postoperative 1.5 cm (range 1.0 cm to 2.3 cm). Excretory urography at 3 months postoperatively showed improved drainage. Of the 51 patients, 35 underwent two or more excretory urograms, demonstrating stable renal function, improved drainage and no evidence of recurrent obstruction. At the last followup visit, each patient was doing well. CONCLUSIONS: Combination of laparoscopic and open procedure in dismembered pyeloplasty offers a simpler, timesaving method in a minimally invasive fashion with low morbidity for patients with ureteropelvic junction obstruction. Ensuring quality of repair, the method provides a minimally invasive alternative with good results. It is worth future clinical application.

[Laparoscopic aid in upper urinary reconstructive operation].

OBJECTIVE: To evaluate the efficacy and feasibility of laparoscopic aid in upper urinary reconstructive operation. METHODS: Fifty-eight patients with ureteropelvic junction obstruction, 5 patients with upper ureter polypous, 2 patients with upper ureter stenosis, and 13 patients with upper ureter lithiasis underwent upper urinary reconstructive operation with laparoscopic aid described as follows:an incision 1 cm long was made, a 10 mm trocar and a 30 degrees laparoscope were wt in, the part with lesion was isolated and resected, and then pyeloplasty or end-to-end anastomosis of ureter was performed. RESULTS: The mean operative time was 33 minutes (25-45 minutes). The mean blood loss was 20 ml (15-25 ml). Complications such as urinary leakage and infection were observed. The double J stent was removed at 1 month after the operation. Follow-up for 3 to 15 months in 20 cases showed alleviation of hydronephrosis. CONCLUSION: An effective and safe method with less wound and operative time, combination of laparoscopic aid and open surgery in upper urinary reconstructive operation helps avoid difficult laparoscopic operation, does not increase trauma of the abdominal wall, and is worth promoting clinically.

[Extraperitoneal laparoscopic radical prostatectomy (report of 5 cases)].

OBJECTIVE: To discuss the clinical experience of laparoscopic radical prostatectomy by extraperitoneal approach. METHODS: Five patients with localized prostate cancer underwent laparoscopic radical prostatectomy by extraperitoneal approach. The surgical procedure included the excision of the prostate, seminal vesicles, ampulla ductus deferentis and part of the bladder neck, followed by urethrovesical anastomosis. RESULTS: All the operations were successful. The mean operation time was 350 minutes (ranging from 270 to 420 mm); the mean estimated blood loss was 480 ml (ranging from 250 to 600 ml). The bowel activity was recovered with 48 hours after surgery. The patients were ambulant between the 2nd and 3rd postoperative days. The mean hospital stay was 8. 5 days (ranging from 7 to 12 days). The 3-8 months follow-up found no incontinence of urine; of the 3 preoperatively potent patients, 2 were able to have sexual intercourse; strictured stoma was reported in only 1 case. CONCLUSION: The extraperitoneal laparoscopic radical prostatectomy, keeping the procedure out of the peritoneal cavity, with small incision and rapid recovery, may be considered as a promising surgical method for patients with localized prostate cancer.

[Seventy degrees lateral decubital trans-abdominal laparoscopic adrenal surgery].

OBJECTIVE: To introduce a new procedure of laparoscopic adrenal surgery. METHODS: Thirty patients with adrenal disease underwent surgery by a 70 degrees lateral decubital trans-abdominal laparoscopic approach, which wa compared with 30 degrees decubital laparoscopic operation in 26 patients. RESULTS: The procedure is superior to open laparotomy. There was significant difference in average operative time (77.2 min vs. 215.7 min), blood lost volume (27.0 ml vs. 94.5 ml), and postoperative complications (13.3% vs. 46.0%). Postoperative feeding time and hospitalization time were shortened markedly. CONCLUSIONS: This modified technique is safe, straightforward, with a good anatomic view during operation. It could be widely adopted for the treatment of benign adrenal disease, especially pheochromocytoma.

Laparoscopic partial nephrectomy for T1a renal tumors is safe and feasible.

BACKGROUND: Some patients with exophytic renal masses less than 4 cm and suboptimal renal function, or a solitary kidney and bilateral renal tumors are considered for laparoscopic partial nephrectomy (LPN), which is feasible for early-stage renal tumors, although it is still considered technically difficult and time consuming. Shortening the time of the operation and renal warm ischemia are required urgently. In this study, we report our initial experiences of LPN, especially with some improved surgical techniques. METHODS: Between July 2005 and October 2009, 74 patients with T(1a) renal tumor were treated by LPN, 39 using transperitoneal approach and 35 using retroperitoneal approach. In all cases, the tumor was removed with a margin of 0.5 cm. We compared glomerular filtration rate (GFR) preoperatively and postoperatively, and renal warm ischemia time between traditional ligature and Hem-o-lok methods. RESULTS: All operations were completed successfully, and there was no conversion to open surgery. Mean operation time was 76 minutes (range, 68 - 120), mean time of renal warm ischemia was 23 minutes (range, 15 - 32), and mean blood loss was 65 ml (range, 40 - 300). No hemorrhage or urine leak was observed in two cases with the collecting system sewn. Thirteen cases used Hem-o-lok to clamp the suture instead of traditional ligature, and mean time of renal warm ischemia was (16.5 ± 2.3) minutes (range, 12 - 18). Mean postoperative hospital stay was 6.3 days (range, 5 - 12). Sixty-seven cases had renal clear cell carcinoma, six papillary renal cell carcinoma, and one renal collecting duct carcinoma. All the tumor margin specimens were negative. The mean follow-up was 30.6 months (range, 3 - 51), and no recurrence or metastasis was observed. CONCLUSIONS: LPN for pT(1) stage renal tumor was safe and feasible. Hem-o-lok instead of traditional ligature to clamp the suture when sewing the renal wound could shorten the warm ischemia time.