Junjie Zhao

Laparoscopic versus open radical cystectomy for elderly patients over 75-year-old: a single center comparative analysis.

Purpose To explore the morbidity, mortality and oncological results of laparoscopic radical cystectomy (LRC) in the elderly patients over 75-year-old in contrast with open radical cystectomy (ORC). Materials and Methods We analyzed 46 radical cystectomies from January 2009 to December 2013 in patients over 75-year-old in our institute, 21 patients in the LRC group and 25 in the ORC group. Demographic parameters, operative variables and perioperative outcome were retrospectively collected and analyzed between the two groups. Perioperative morbidity and mortality were categorized as early (within 90 days after surgery) or late (more than 90 days) according to the time of occurrence. Results Patients in both groups had comparable preoperative characteristics. A significant longer operative time (418 vs. 337 min, p = 0.018) and less estimated blood loss (400 vs. 500 ml p = 0.038) were observed in LRC group compared with ORC group. Infection and ileus were the most common early complications after surgery. Patients underwent ORC suffered from significantly more postoperative ileus (28.0% vs. 4.8%, P = 0.038) and infection (40% vs. 9.5%, P = 0.019) than LRC group within 90 days after surgery. The mortality rate was 4.7% (1/21) and 4% (1/25) for LRC group and ORC group respectively. At a median follow-up of 21 months (range 2–61 months), the Kaplan-Meier survival curves and log-rank analysis demonstrate that there were no significant differences between the LRC and ORC groups in the 3-year overall, cancer-specific, or recurrence-free survival rates. Conclusions It is suggested that LRC should be recommended as the primary intervention to treat muscle invasive or high risk non-muscle invasive bladder cancer in elderly patients with a relative long life expectancy.

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.

Minimally Invasive Surgery for Patients with Bulky Bladder Stones and Large Benign Prostatic Hyperplasia Simultaneously: A Novel Design

Objective: To determine the efficacy and safety of a novel minimally invasive design for treating bulky vesical calculi and large benign prostatic hyperplasia (BPH) simultaneously. Methods: 76 patients with large bladder stones (>4 cm) and large BPH (≥50 cm3) were treated from August 2008 to January 2011. 38 patients (group 1) underwent transurethral cystolithotripsy followed by transurethral resection of the prostate (TURP), 38 patients (group 2) received percutaneous cystolithotripsy within a laparoscopic entrapment bag and TURP by two surgeons simultaneously. 72 patients were followed up for 1 year. Patient demographics, perioperative parameters and follow-up data were compared. Results: Patient baseline characteristics were comparable in the two groups. In group 1, 3 patients converted to open surgery and received blood transfusion, 4 patients had postoperative fever, 2 had residual stones and 1 developed urethral stricture postoperatively. In group 2, the mean total operative and the operative times for stone management were 71.6 and 30.1 min, respectively, the mean hemoglobin decrease was 0.80 g/dl, no patients received blood transfusion and no complications occurred, significantly superior to group 1. Conclusions: Percutaneous cystolithotripsy using a laparoscopic entrapment bag associated with TURP by two surgeons simultaneously is a highly effective, safe and minimally invasive method for managing large vesical calculi and large BPH.

A Pilot Study of Vela Laser for En Bloc Resection of Papillary Bladder Cancer

Micro‐Abstract Transurethral resection of bladder tumors is associated with perioperative or postoperative complications, and an “incise and scatter” procedure contradicts basic oncologic principles. The present study introduces the Vela laser, a new type of thulium laser with a 1.94‐&mgr;m wavelength, for en bloc resection of bladder tumors. The pilot experience found the Vela laser could preserve the muscle layer and was effective, feasible, and safe for patients with bladder tumors. Introduction: The present study evaluated the safety and efficacy of the Vela laser for en bloc resection of papillary bladder tumors. Materials and Methods: From January 2013 to August 2014, 38 patients underwent en bloc resection with the Vela laser and a 26F continuous flow resectoscope or 18F flexible cystoscope. Random cold forceps biopsy samples were also taken. The total operation time, pathologic result, and intraoperative and postoperative complications were recorded. Each patient was followed up for ≥ 1 year. Results: The average total operation time was 23 minutes. The en bloc resection of all tumors was successful, with 2 cases located at the bladder dome requiring the use of a flexible cystoscope for better management. No complications occurred during or after surgery. All resected tumors were intact with the detrusor muscle layer and architecture available for pathologic evaluation. One patient with stage T2b tumor underwent laparoscopic cystectomy 1 week after the initial surgery. At a median follow‐up period of 21.8 months, the recurrence rate at 12 months was 21.6% (8 of 37). Conclusion: The results of our study have shown that the Vela laser is an effective, feasible, and safe thulium laser for en bloc bladder tumor resection. It was associated with negligible complications and allows accurate pathologic evaluation. The Vela laser can serve as an alternative treatment method for nonmuscle‐invasive bladder cancer or infiltrating tumor.

Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent copy number variation in IPO11 and prognostic significance of importin-11 overexpression on poor survival

Non-muscle-invasive bladder cancer (NMIBC) often has a worse prognosis following its progression to muscle-invasive bladder cancer (MIBC), despite radical cystectomy with pelvic lymph node dissection combined with chemotherapy. Therefore, the discovery of novel biomarkers for predicting the progression of this disease and of therapeutic targets for preventing it is crucial. We performed whole-exome sequencing to analyze superficial tumor tissues (Tsup) and basal tumor tissues (Tbas) from 3 MIBC patients and identified previously unreported copy number variations in IPO11 that warrants further investigation as a molecular target. In addition, we identified a significant association between the absolute copy number and mRNA expression of IPO11 and found that high importin-11 expression was correlated with poor 3-year overall survival (OS), cancer-specific survival (CSS) and cancer-free survival (CFS) compared with low expression in the BCa patients. Importin-11 overexpression was also an independent risk factor for CSS and CFS in the BCa patients. Our study has revealed that IPO11 copy number amplification contributes to its overexpression and that these changes are unfavorable prognostic factors in NMIBC. Thus, IPO11 copy number amplification and importin-11 overexpression are promising biomarkers for predicting the progression and poor prognosis of patients with NMIBC.

The Transplantation Operation and Its Surgical Complications

Over the past decades, the outcomes of kidney transplantation have improved markedly due to advancements in prevention and treatment of acute rejection episodes, management of posttransplant complications and better knowledge of immunosuppressive drugs. As a result, transplantation has become the mainstay and preferred treatment for patients of all ages with end-stage renal disease. However, the surgical technique for renal transplantation has changed little from the original pelvic operation described in 1951 by Kuss et al. It seems the operation has been standardized and there is little need for further discussions over the topic. In fact, the argumentation on surgical technique has never ceased since its birth, for optimization of the surgical outcomes, many aspects of operative techniques have been modified and novel techniques have been invented. In modern immunosuppressive era, the pattern of surgical complications has evolved and gains some fresh features. In this chapter, we will review the standard operative procedures performed today and introduce the updated surgical techniques as well. Meanwhile, the characteristics of major surgical complications and the evolvement of their diagnosis and treatment will be expatiated on. After all, the surgical operation is invariably the key of a successful transplantation; surgical techniques are constantly related to the morbidity and mortality of the patients.

Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p = 0.001), progression-free (median, 19.7 vs. 27.9 months, p = 0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p = 0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

Importin-11 overexpression promotes the migration, invasion, and progression of bladder cancer associated with the deregulation of CDKN1A and THBS1

OBJECTIVES We recently determined that a novel oncogene, IPO11 from 5q12, participates in bladder cancer (BCa) progression. However, the biological function of IPO11 and the molecular mechanisms through which it contributes to BCa progression remain unclear. The aim of this study was to investigate the role of IPO11 in BCa aggressiveness and elucidate the molecular mechanisms underlying its effects in BCa. MATERIALS AND METHODS The mRNA expression levels of IPO11 in BIU-87, RT4, UMUC3, EJ, 5637, T24, J82, and HT-1376 cell lines were determined using quantitative real-time polymerase chain reaction. Expression of importin-11 was detected in 134 formalin-fixed and paraffin-embedded (FFPE) BCa tissues and 10 paired nonneoplastic bladder tissue specimens by immunohistochemistry. The copy number of IPO11 was examined in 25 FFPE BCa specimens using fluorescent in situ hybridization. The effects of IPO11 on migration, invasion, and cell proliferation were investigated in EJ and 5637 cell lines using RNA interference. Potential molecular mechanisms were investigated using whole transcriptome sequencing and bioinformatic approaches in EJ cells and IPO11-silenced EJ cells and verified using quantitative real-time polymerase chain reaction. RESULTS Endogenous IPO11 mRNA was highly expressed in 6 invasive BCa cell lines (EJ, HT-1376, UMUC3, 5637, J82, and T24) but had a low expression in the noninvasive BCa cell line BIU-87 and the papillary BCa cell line RT4. Immunohistochemical staining revealed that 87 (64.9%) of 134 FFPE BCa tissues displayed importin-11 overexpression. Moreover, importin-11 overexpression was positively associated with increased tumor stages and tumor grades, lymphatic invasion, and lymph node metastasis. Furthermore, importin-11 overexpression was detected in 100% (14/14) of BCa tissues with IPO11 amplification, and IPO11 amplification was not observed in 2 additional BCa tissues with importin-11 overexpression. Small interfering RNA-mediated knockdown of IPO11 is sufficient to inhibit the motility and invasiveness of EJ and 5637 cells. IPO11 knockdown also inhibited cell proliferation in EJ cells, whereas this was not observed in 5637 cells or the in vivo experiments. Using whole transcriptome sequencing, we found that 22 genes (including IPO11) were differentially expressed in IPO11-silenced EJ cells compared with wild-type EJ cells, 4 of which were upregulated, and 18 of which were downregulated. KEGG pathway enrichment analysis of the significantly differentially expressed genes showed that the proteoglycans in cancer pathway (pathway Id: hsa05205) was most significantly enriched among 10 genetically altered pathways and referred to 6 significantly altered genes (CDKN1A, HBEGF, PTK2, THBS1, CCNG2, and EGR1). The next 3 most significantly enriched pathways in order were the p53, ErbB, and BCa pathways. CDKN1A and THBS1 were the most 2 frequently covered genes and were involved in 9 and 6 pathways, respectively. They were also 2 key proteins in the BCa pathway (pathway Id: hsa05219) that were downregulated in IPO11-knockdown EJ cells compared with wild-type EJ cells. CONCLUSIONS Importin-11 overexpression can promote BCa cell invasiveness, probably associated with the deregulation of CDKN1A and THBS1 primarily through the activation of the proteoglycans in cancer pathway and the classical BCa pathway. Importin-11 may be a useful target through which the progression of noninvasive BCa to invasive BCa can be blocked.

AB100. Laparoscopic ureteral reimplantation underneath broad ligament tunnel for female vesicoureteral stenosis: a technical innovation

Purpose In order to anatomically reconstruct the ureteral stenosis, we present a novel technique for laparoscopic ureteral reimplantation. Patients and methods Three young females, who were diagnosed as hydroureteronephrosis caused by congenital vesicoureteral junction obstruction, were treated by laparoscopic ureteral reimplantation with a tunnel underneath the broad ligament. Results Surgery was performed successfully without conversion to open surgery. No major intraoperative or postoperative complications occurred. The mean postoperative follow-up was 38, 33 and 26 months respectively. The operative time was between 220 and 260 minutes. The mean estimated blood loss was less than 20 mL. Subsequent imaging performed 3 months after surgery revealed relief of hydroureteronephrosis for all patients. Patients all gave birth to healthy neonates and showed normal urinary tract sonogram and urine analysis during gestation period. Conclusion Laparoscopic ureteral reimplantation with a tunnel underneath the broad ligament tunnel is safe, effective, allowing for anatomical reconstruction of ureter defects, however. A larger clinical sample and longer follow-up period will be needed for fully validation of this technique.

The complete mitochondrial genome sequence of the prostate adenocarcinoma rat R3327

Abstract The prostate adenocarcinoma of the Copenhagen rat (R3327) is recognized as a suitable model for human prostate carcinoma. In this study, we sequenced its complete mitogenome and total length of the genome was 16,310 bp (GenBank Accession Number KM820831). It contains 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into prostate adenocarcinoma disease.