LIMD2 promotes tumor proliferation, invasion, and epithelial-mesenchymal transition in clear cell renal cell carcinoma.

LIMD2 was found upregulated in various tumors and metastatic samples and associated with a poor prognosis. But the role of LIMD2 in clear cell renal cell carcinoma (ccRCC) remains elusive. The expression of LIMD2 in ccRCC was analyzed using cohort data downloaded from TCGA and ICGC databases. In vitro and in vivo experiments were then conducted to study the biological role of LIMD2 in ccRCC and explore the possible mechanism. The results indicated that LIMD2 was overexpressed and correlated with a poor outcome in ccRCC. LIMD2 promoted the malignancy of ccRCC both in vitro and in vivo. LIMD2 induced epithelial-mesenchymal transition (EMT) via activating the ILK/Akt pathway in ccRCC. In conclusion, LIMD2 is overexpressed and promotes proliferation, invasion, and EMT in ccRCC, which may serve as a potential novel therapeutic target for ccRCC.

Determination of the Safe Surgical Margin for T1b Renal Cell Carcinoma.

PURPOSE: To determine the rational surgical margin for pathological T1b renal cell carcinoma (RCC). MATERIALS AND METHODS: This retrospective study included surveys of 60 patients with T1bN0M0 RCC who underwentradical nephrectomy (RN, n = 40) or partial nephrectomy (PN, n = 20) between October 2008 and December2014 at the Sun Yat-sen Memorial Hospital affiliated with Zhongshan University. Specimens were collectedfrom 6 sites at the tumour periphery for RN and PN, and at suspected sites on the tumour surface for PN in addition.The histological subtype, pathological grade, surgical margin, pseudocapsule completeness, distribution of satellitefoci, and largest distance between the extra-pseudocapsule lesion and primary tumour (DEP) were evaluated. Thispaper will analyse the relationships between these factors. RESULTS: The positive surgical margin rate was 10% in patients undergoing PN. The study found no significantrelationships between the incidence of satellite foci and tumour diameter, Fuhrman grade, or histological subtype(all P > 0.05). However, male sex, positive surgical margins, and an incomplete pseudocapsule were associatedwith the incidence of satellite foci (P < 0.05). Cases with satellite foci tended to show positive surgical margins.The DEP was <1.0 mm for all tumours, but there were no significant relationships between the DEP and the tumourdiameter, pathological grade, or histological subtype (P > 0.05). CONCLUSION: In T1b RCC, a 1-mm surgical margin would be sufficient to attain integrated resection of the primarytumour and its cancerous tissue beyond the pseudocapsule. PN was insufficient to prevent a positive surgical margin,most likely due to the presence of satellite foci.

Angiokeratoma of Fordyce response to long pulsed Nd:YAG laser treatment.

Angiokeratoma of Fordyce can be easily diagnosed by their typical erythra and cured by varied therapeutic methods including surgery, electrocoagulation, cryotherapy, or various laser systems. Which are the optimal therapeutic methods? There are no consentaneous opinions in the reported articles. We present our characteristic treatment with the application of long pulsed neodymium-dopedyttrium-aluminum-garne (lpNd:YAG) laser in the treatment of angiokeratoma of Fordyce. A 1064 nm lpNd:YAG laser (spot size: 5 mm/7 mm, energy:90-130 J/cm(2) , and pulse duration: 10-20 ms.) was used to treat the patient's lesions. The desirable clinical endpoint of the treatment was lesions shrunk and turned pallor immediately after the irradiation. The treatment interval was at least 8 weeks. Of the 11 patients, 9 of them were cured and 2 of them were improved. The mean treatment sessions were 2.2 times. None of them had a scar formation and any other side effects. All of them were satisfied with the treatment results. We conclude that angiokeratoma of Fordyce responded well to lpNd:YAG laser treatment. It provided a simple, rapid, and no bleeding treatment in treating Angiokeratoma of Fordyce.

CAV-1 contributes to bladder cancer progression by inducing epithelial-to-mesenchymal transition.

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) is a critical step in tumor metastasis. CAV-1 has been shown to be an oncogene in bladder cancer. However, little is known about the relationship between CAV-1 and EMT in bladder cancer metastasis. METHODS: Immunohistochemical analysis was carried out retrospectively on tumor samples from patients treated for bladder cancer. CAV-1 and E-cadherin expression levels were measured and correlated with clinical features of tumor grade and metastasis. EMT was assessed in bladder cancer cell lines (T24, UMUC3, HT1376, and 5637) using wound healing and in vitro transwell invasion assays, and small interfering RNA was used to knock down CAV-1 and Slug expression. RESULTS: In this study, we show that increased CAV-1 expression induces bladder cancer cell migration and promotes the EMT, which was determined by the reduction of E-cadherin expression and the induction of N-cadherin and vimentin expression. Knockdown of CAV-1 expression with specific small interfering RNA reduced cell migration and EMT. Mechanistically, CAV-1-induced expression of the transcription factor, Slug. Slug knockdown abolished the CAV-1-induced EMT in bladder cancer cells. We further show that Slug expression is mediated by the CAV-1 regulation of the PI3K/AKT signaling. In addition, positive CAV-1 expression was significantly correlated with negative E-cadherin expression, as determined by immunohistochemistry analysis in bladder cancer tissues. CONCLUSIONS: Our results suggest that CAV-1 promotes invasive phenotypes in bladder cancer cells by inducing EMT through up-regulation of Slug expression, which occurs through activation of the PI3K/AKT signaling pathway. This new role for CAV-1 in promoting bladder cancer metastasis presents CAV-1 and related pathways as potential therapeutic targets in invasive bladder cancer.

Investigation on the indication of ipsilateral adrenalectomy in radical nephrectomy: a meta-analysis.

BACKGROUND: With a trend that renal tumors are being detected at an earlier stage, classical radical nephrectomy is being reconsidered. More conservative techniques are being proposed. To clarify the indication for synchronous adrenalectomy in radical nephrectomy for renal cell carcinoma which has been questioned since the 1980s, this study evaluates the role of adrenalectomy and recommends a new indication for adrenalectomy in renal cell carcinoma. METHODS: A systemic search was performed, using PubMed and Google Scholar, of all English language studies published up to March 2012 that compared adrenalectomy with adrenal-sparing surgery, in surgery for renal cell carcinoma. We assessed preoperative imaging for adrenal involvement and the relationship of tumor location with adrenal metastases. Twenty-one studies (20 retrospective and 1 prospective) involving 11 736 patients were included. RESULTS: The mean incidence of ipsilateral adrenal involvement from renal cell carcinoma was 4.5%. Synchronous adrenalectomy did not alter survival (hazard ratio (HR) = 0.89, 95% confidence interval (CI) 0.67 - 1.19, P = 0.43; odds ratio (OR) = 1.10, 95%CI 0.84 - 1.44, P = 0.49). Upper pole tumors were not associated with a higher incidence of ipsilateral adrenal metastases. Pooled preoperative imaging: sensitivity, specificity, positive predictive value and negative predictive value were 92% (95%CI 0.84 - 0.97), 95% (95%CI 0.93 - 0.96), 71.6% and 98.5% respectively. CONCLUSIONS: Adrenal involvement from renal cell carcinoma is rare, even in advanced tumours. Synchronous adrenalectomy does not offer any benefit, even for "high risk" patients. We suggest that only patients with a positive preoperative adrenal finding on preoperative imaging for a solitary adrenal metastasis should undergo adrenalectomy as part of the radical nephrectomy.

[Application of modified single port laparoscopic radical cystoprostatectomy and orthotopic ileal neobladder].

OBJECTIVE: To evaluated the feasibility and therapeutic effect of laparoscopic-endoscopic single-site surgery (LESS) for radical cystoprostatectomy and orthotopic ileal neobladder. METHODS: Between November 2008 and August 2009, 8 male patients with bladder cancer underwent modified single port laparoscopic cystoprostatectomy and orthotopic ileal neobladder with a home-made multichannel port made up of two stretchable rings and a surgical glove with trocars and valves attached to its fingers. A 4 - 5 cm midline incision was made in lower abdomen and the multichannel port placed into this incision. Laparoscopic instrument was extended through the multichannel port. Another port was placed at the umbilicus site for laparoscope. The investigators performed the modified single port transperitoneal technique neobladder extracorporeally and urethro-pouch anastomosis under laparoscopy with a slipknot running suture technique. The perioperative and postoperative data were collected and analyzed prospectively. RESULTS: In all cases, no conversion into conventional laparoscopic or open surgery was necessary. The mean operative duration, including extended lymph node dissection, was 399 min (range: 355 - 455 min). Mean estimated blood loss was 154 ml (range: 90 -210 ml). The mean postoperative hospital stay was 15 d (range: 14 - 18 d). No peri-operative mortality was reported. One case had delirium 2 days postoperatively and there was no port-related complication. The pathological report confirmed surgical margins were tumor-free for all cases. The average number of removed lymph node was 20. The mean follow-up period was 6.1 months (range: 2.0 -10.0 months). All patients remained disease-free until the last follow-up. CONCLUSIONS: With a reduction of 4 ports, modified single port laparoscopic radical cystectomy with orthotopic ileal neobladder is technically feasible with a low complication rate. Our initial outcome is encouraging, but additional work and a further follow-up are warranted to critically compare the oncological outcome with open surgery.

[Inhibition and significance of pigment epithelium-derived factor in the development and metastasis of prostate cancer].

OBJECTIVE: To study the inhibition and significance of pigment epithelium-derived factor (PEDF) in the development and metastasis of prostate cancer. METHODS: The expression of PEDF was examined in the normal prostate tissue, benign prostatic hyperplasia, prostate cancer tissue and prostate cancer cell lines, PC-3 and Lncap by immunohistochemical SP method and Western blot. In combination with clinical data, statistical analysis was performed to evaluate the relation of the expression level of PEDF in prostate cancer and the relationship between different histological grades of prostate cancer. RESULTS: In normal prostate tissue and benign prostate tissue, the expression of PEDF were elevated and it was far higher than the prostate cancer and prostate cancer cell line. The expression of PEDF and the pathological grade of prostate cancer were related to the differentiated carcinoma of prostate tissue, and the expression level of PEDF in poorly differentiated carcinoma below the highly differentiated carcinoma of prostate cancer. In metastatic prostate cancer, the expression of PEDF was lower than that of prostate cancer without metastasis (12% vs 43.1%). CONCLUSION: The expression of PEDF and the incidence of prostate cancer have a negative correlation. The lower grade of prostate cancer cells, the less the tissue expression of PEDF and the higher tendency of invasion and metastasis.

[Laparoscopic radical cystectomy with orthotopic ileal neobladder: report of 108 cases].

OBJECTIVE: To analyze the effects, complication, and outcome of laparoscopic radical cystectomy. METHODS: 108 patients with bladder cancer, 96 males and 12 females, aged 61 (36 - 81) underwent laparoscopic radical cystectomy with orthotopic ileal neobladder. Five-port transperitoneal approach was applied. The surgical procedure included standard laparoscopic pelvic lymphadenectomy, radical resection of bladder, extracorporeal formation of ileal pouch; extracorporeal implantation of ureters; and laparoscopic urethra-neobladder anastomosis. Erectile nerve sparing procedure was performed for 26 cases. The patients were followed up for 1 - 53 months. RESULTS: The median operation time was 330 min, and the median blood loss was 320 ml. Conversion to open surgery was not necessary in any of the patients. There was no peri-operative mortality. The complication rate was 18.5% (20/108). Surgical margins were tumor free for all cases. The day-time and night-time continence rates were 90.7% and 82.6% respectively in 6 months postoperatively. 10 of the 26 patients undergoing erectile nerve-sparing procedure had potency for intercourse. Follow-up showed 5 cases with local recurrence, 1 case with trocar site seeding and 6 cases with distant metastasis, 8 of the patients died of tumor-related disease and 3 died of diseases not related to tumor. CONCLUSION: Laparoscopic radical cystectomy with extracorporeal formation of orthotopic ileal neobladder is a feasible technique with low morbidity and acceptable neobladder function.

Laparoscopic radical cystectomy with orthotopic ileal neobladder in the female: report of 14 cases.

BACKGROUND: Bladder carcinoma is the most common malignant urological tumor in China. We present our preliminary experience and results of laparoscopic radical cystectomy (LRC) with orthotopic ileal neobladder in female patients with bladder carcinoma. METHODS: From February 2003 to February 2008, 14 female patients with bladder carcinoma underwent LRC with orthotopic ileal neobladder. Nine of these patients underwent hysterectomy and ovariectomy, and the other 5 had preservation of the uterus and ovarian appendage. Standard bilateral pelvic lymphadenectomy was followed by radical cystectomy that was completed laparoscopically with hysterectomy and ovariectomy when needed. The tumor was removed by a 4 - 5 cm lower midline abdominal incision, followed by the construction of ileal neobladder and the extracorporeal anastomosis of ureter-neobladder. The neobladder was anastomosed to the urethral stump under a laparoscope. RESULTS: The mean operative time and blood loss in the 14 patients were 350.2 minutes and 349.8 ml, respectively. Postoperative complications included uretero-pouch anastomotic stricture in 1 patient and pouch-vaginal fistula in 1 patient. Follow-up time of all patients ranged from 3 to 60 months, and 12 patients were followed up for more than 6 months and achieved micturition in half a year. One patient had occasional day-time urinary incontinence and 2 had night-time incontinence. Two patients who had undergone hysterectomy and ovariectomy had voiding difficulties after one year, which was treated by intermittent self-catheterization. The mean volume of the neobladder and the residual urine were 333.6 ml and 31.2 ml, respectively. Surgical margins were tumor free for all patients. One patient had bone metastasis and died 11 months after the operation. CONCLUSIONS: LRC with orthotopic ileal neobladder in female patients is a technically feasible, safe and mini-invasive procedure with a low morbidity and acceptable neobladder function. Long-term follow-up is required to confirm the neobladder function and oncological outcomes.

[Compare of laparoscopic and open surgery for radical cystectomy with orthotopic ileal neobladder].

OBJECTIVE: To compare the clinical therapeutic effect and complications of laparoscopic radical cystectomy with orthotopic ileal neobladder (LRC-INB) with open radical cystectomy with orthotopic ileal neobladder (ORC-INB). METHODS: A total of 171 patients were evaluated, including 63 cases with ORC-INB and 108 cases with LRC-INB from June 1994 to May 2007 at our institution. The parameters analyzed included perioperative data, postoperative complications, new bladder function and effect of tumor control. RESULTS: There was no significant difference in demographic characteristics of patients between these 2 groups. The mean operating time was 330 min in the LRC group and 310 min in the ORC group (P > 0.05). The mean blood loss was 320 ml in the LRC group and 1100 ml in ORC group (P < 0.001). The mean oral intake after operation was 2.4 days for LRC group and 4.5 days for ORC group (P < 0.001). No perioperative death was occurred in both groups. The complication rate was 18.5% in LRC group, while 30.0% in ORC group (P < 0.05). Twelve months after operation, the day-time and night-time continence rate were 90.7% and 82.6% for the LRC group, 88.3% and 81.6% for the ORC group respectively (P > 0.05). There was no significant difference of VOL, pressure and residual urine volume (RUV) of neobladder between these 2 groups. Surgical margin were tumor free for 107 cases except one T4 case in laparoscopic group had positive margin (P > 0.05). The mean number of removed lymph node were 12 and 8 in LRC and ORC group respectively (P < 0.05). The 2 years tumor free survival rate of the same stage or grade was no significant different (P > 0.05). CONCLUSIONS: LCR had advantages of less blood loss, shorter oral intake time, less postoperative complications, comparable continent rate and short-term tumor control with ORC. Long-term follow up is needed to confirm the oncological outcome.

[Needle laparoscopic varicocelectomy].

OBJECTIVE: We evaluated our method and effects of needle laparoscopic varicocelectomy for the treatment of varicocele. METHODS: 72 patients (105 lateral) diagnosed varicocele were performed laparoscopic varicocelectomy under epidural combined intravenous anesthesia from Feb, 2003 to Apr, 2005. Two 2 mm incisions and one 5 mm incision were made on the midline of lower abdomen, by which two 2 mm trocars and one 5 mm trocar were introduced. Vessel-sealing device (Ligasure) was used to seal the internal spermatic veins. RESULTS: All operations were completed successfully. Mean operation time was 15 minutes unilateral and 21 minutes bilateral. The patients were hospitalized for 3 to 5 days after procedure. Follow-up was scheduled for 6 to 12 months and there was no recurrence. CONCLUSION: Needle laparoscopic varicocelectomy gives favorable effect with minimal invasion, rapid recovery, which is the best choice for the treatment of varicocele.

Laparoscopic radical cystectomy with orthotopic ileal neobladder: report of 33 cases.

BACKGROUND: The laparoscopic radical cystectomy (LRC) with orthotopic ileal neobladder is now applied to treat invasive bladder cancer, however, it has not been well codified and illustrated. We describe in this paper a technique step by step that we have developed in 33 patients and achieved excellent results. METHODS: The surgical procedure can be divided into eight steps: laparoscopic pelvic lymphadenectomy and mobilization of the distal ureters; exposing Denonvillier's space and the posterior aspect of prostate; exposing retropubic space and anterior surface of the bladder; dividing the lateral pedicles of the bladder and the prostate; dividing the apex of the prostate; extracorporeal formation of the ileal pouch; extracorporeal implantation of the ureters; and laparoscopic urethra-neobladder anastomosis. This operation was performed in 33 patients, 29 males and 4 females, with muscle invasive bladder cancer between December 2002 and September 2004. RESULTS: The operating time was 5.5-8.5 hours with an average of 6.5 hours; the estimated blood loss was 200-1000 ml with an average of 460 ml. The surgical margins of the bladder specimen were negative in all patients. There was no evidence of local recurrence at follow-up of 1-21 months in all the patients. However lymph node metastases were found in one case at 9 months postoperatively. Most of patients achieved urine control 1 to 3 months after surgery. The daytime continence rate was 94% (31 cases) and nighttime continence rate was 88% (29 cases). Urodynamic evaluation was performed between 3 and 6 months postoperatively for all cases. The mean value of neobladder capacity was (296 +/- 37) ml. The mean value of maximum flow rate was (18.7 +/- 7.1) ml/s. The mean residual urine volume was (32 +/- 19) ml. In all cases, excretory urography at 1 to 2 months postoperatively demonstrated slightly dilated upper urinary tracts without ureteral obstruction, which resolved at follow up. Cystography showed neobladders being similar in shapes to normal. Two small ureteral nipples with intermittently efflux of urine were observed at cystoscopy in most patients. Postoperative complications occurred in 6 of 33 patients (18%), including pouch leakage in 2 cases, pelvic infection in 1, partial small bowel obstruction in 2 and neobladder-vaginal fistula in 1. CONCLUSIONS: The LRC with orthotopic ileal neobladder is a feasible option for bladder cancer when radical cystectomy is indicated. The extracorporeal formation of the ileal pouch and ureteral implantation through a small lower midline incision can simplify the complexity of the procedures, shorten the duration of surgery and reduce the medical expenses.

[Expression of extracellular matrix metalloproteinase inducer in human bladder transitional cell carcinoma].

BACKGROUND & OBJECTIVE: Matrix metalloproteinases(MMPs) play critical roles in the process of tumorigenesis, tumor invasion and metastasis. Extracellular matrix metalloproteinase inducer (EMMPRIN) derived from cancer cell can induce stromal fibroblasts to synthesize MMPs, which advances the invasion and metastasis of cancer. This study was designed to investigate the roles of EMMPRIN in the tumorigenesis, invasion and metastasis of bladder carcinoma by detecting the expression of EMMPRIN in human normal and carcinomatous bladder tissues. METHODS: The expression of EMMPRIN was examined in 45 bladder carcinoma tissues from 45 patients and normal bladder mucosa from 9 persons by immunohistochemistry SP method. The relationship between EMMPRIN expression and clinicopathologic parameters was analyzed. RESULTS: EMMPRIN protein was localized at membrane and cytoplasm of carcinomatous epithelial cell, but was not expressed in normal bladder epithelial or tumor stromal cell. The overall positive rate of EMMPRIN in 45 cases of bladder carcinoma was 73%. The positive rates of EMMPRIN in grade II, grade III and recurrent carcinomas were 84%, 85%, and 100%, respectively, significantly higher than those in grade I and non-recurrent carcinomas (14% and 56%, respectively) (P< 0.05). The intensive positive rate of EMMPRIN in lymph node metastasis group (86%) was significantly higher than that in no lymph node metastasis group (24%) (P< 0.05). CONCLUSION: EMMPRIN was overexpressed in human bladder transitional cell carcinoma, and related to the malignant degree and recurrence. It could be a useful indicator for the assessment of potent invasion and metastasis of bladder carcinoma.