Stress-activated kinase pathway alteration is a frequent event in bladder cancer.

OBJECTIVES: The stress-activated MAP kinases (SAPK) signaling pathways play a critical role in the cellular response to toxins and physical stress, mediate inflammation, and modulate carcinogenesis and tumor metastasis. The stress-activated MAP kinases (MAPK) c-Jun N-terminal kinase (JNK) and p38 are activated upon phosphorylation by a widely expressed and conserved family of upstream MAP kinase kinases (MAP2K). Signaling mediated by p38 and JNK has well-established importance in cancer, yet the contribution of this pathway in urothelial bladder cancer is not understood. This study evaluated stress-activated MAP kinase pathway expression in cell lines derived from human urothelial carcinomas. MATERIALS AND METHODS: Total protein lysates from a panel of human urothelial bladder cancer cell lines (RT4, T24, UMUC-3, J82, 5637, 253J, and 253J-BV) were analyzed by immunoblotting for the JNK and p38 MAPKs, as well as MKK3, MKK4, MKK6, and MKK7. Quantitative real time PCR was utilized to determine mRNA expression levels of the MAP2Ks. Stress stimuli (sorbitol, hydrogen peroxide, and UV irradiation) were used to active p38, which was measured by phospho-antibody. RESULTS: Although protein levels were variable, all cell lines expressed p38 and JNK. On the other hand, with the exception of the well-differentiated cell line RT4, each cell line had a reduction or absence of expression of one or more MAP2K. 253J and 253J-BV exhibited no expression of MKK6, even when an excess of protein was queried. mRNA levels indicated that both transcriptional and post-transcriptional mechanisms are involved in the regulation of MAP2Ks. Decreased MAP2K expression correlated with decreased ability to activate p38 in response to stress stimuli. CONCLUSIONS: Aberrant MAP2K protein expression indicates that altered cellular signal transduction mediated via JNK and p38 may be common in bladder cancer. Down-regulation of MAP2Ks likely occurs at both the transcriptional and post-transcriptional levels. Consistent with the known function of p38 and JNK in apoptosis, defects in normal pathway function caused by decreased expression of upstream MAP2Ks may provide a survival advantage to bladder cancer cells. Further investigations should focus on identifying a functional role for these pathways in bladder cancer development.

Paediatric robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendicovesicostomy (RALIMA): feasibility of and initial experience with the University of Chicago technique.

OBJECTIVE: •To present the first series of complete intracorporeal robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendico-vesicostomy (RALIMA) in a paediatric population. PATIENTS AND METHODS: • From February to November 2008, six patients with neurogenic bladder secondary to spina bifida (status post corrective spine surgery) were selected to undergo RALIMA by a single surgeon (MSG) at the University of Chicago Medical Center. • Patients had constipation, day and night-time incontinence, with recurrent urinary tract infection (UTI), and failed attempts at anticholinergic therapy and clean intermittent catheterization. All had low-capacity bladders with poor compliance and high leak point pressures. • Preoperative bowel preparation was not performed. Mean follow-up is 18 months. RESULTS: • One patient required conversion to open ileal augmentation because of failure to progress and another underwent augmentation ileocystoplasty without appendico-vesicostomy. The average age of patients was 9.75 years (range 8-11 years). • Average operative time was 8.4 h (range 6-11 h). There were no intraoperative complications. One patient had a postoperative wound infection, one had a lower extremity venous thrombus, and another had temporary unilateral lower extremity paresthesia that has resolved. Three patients required revision of their stoma at the skin-level. • Perioperatively, patients only required oral analgesia for 24-36 h (excluding one patient with paralytic ileus), started on liquid diet after 7.5 hours (range 6-10 h), on regular diet after 24 h (range 12-36 h) and were discharged home within 7 days. • Postoperatively, patients demonstrated no leak on follow-up cystogram, and were catheterizing per apendico-vesicostomy (three patients by 6 weeks) or urethra (1 patient at 4 weeks). • All patients now have day and night-time continence with no UTIs, and bladder capacity of 250-450 mL. CONCLUSION: • While longer follow-up will be necessary to see if these results are durable, this series demonstrates that RALIMA is a safe, feasible and effective procedure in the short term, with the possible added benefits of reduced analgesia, shorter recovery time and improved aesthetic appearance.

Evolution of open radical retropubic prostatectomy--how have open surgeons responded to the challenge of minimally invasive surgery?

INTRODUCTION: With the advent of minimally invasive surgery (MIS) for treating urologic malignancies, emphasis has been placed on reducing patient morbidity and resuming normal activity. We sought to clarify whether open surgeons (OS) have modified their techniques, surgical equipment, and perioperative management in response to this trend. METHODS: A survey sent to all members of the Society of Urologic Oncology assessed changes that OS performing radical retropubic prostatectomy have made in analgesia, operative technique, perioperative management, and follow-up patterns. We also assessed OS sense of competition from MIS. Surgeon perception of the influence MIS had on these changes was scored from 0 to 4 (0 = not at all, 1 = slightly, 2 = moderately, 3 = greatly, 4 =completely). Overall and major influence by MIS included scores 1-4 and 3-4, respectively. RESULTS: Reduced radical retropubic prostatectomy (RRP) case volume because of MIS competition was reported by 20 OS (24%), with 27 OS (32%) starting to perform MIS, and 20 (24%) doing mostly/exclusively MIS. MIS has influenced OS to reduce incision length (overall influence 56%/major influence 33%), operative time (40%/12%), blood loss (31%/17%), and transfusion rate (33%/14%). MIS has influenced OS to use new instruments (48%/44%) or loupes (20%/9%), modify dissection (45%/31%) or anastomotic technique (14%/12%), and increase the use of hemostatic agents (48%/19%). MIS has reduced convalescence in OS patients by reducing length of stay (52%/28%), time to a regular diet (40%/18%), duration of drain (21%/16%) and Foley (32%/15%), time to return to work (49%/25%), and exercise (44%/21%). MIS has changed follow-up of OS patients by increasing the use of clinical pathways (14%/9%) and validated questionnaires (22%/13%). CONCLUSIONS: To date, the influence of MIS on the OS has not been comprehensively assessed. This survey finds that OS report that MIS serves as major competition to the open technique and that it has influenced them to modify their surgical technique, reduce convalescence, and alter follow-up recommendations.

Wolffian duct derivative anomalies: technical considerations when encountered during robot-assisted radical prostatectomy.

BACKGROUND: Although malformations of the genitourinary tract are typically identified during childhood, they can remain silent until incidental detection in evaluation and treatment of other pathologies during adulthood. The advent of the minimally invasive era in urologic surgery has given rise to unique challenges in the surgical management of anomalies of the genitourinary tract. OBJECTIVE: This article reviews the embryology of anomalies of Wolffian duct (WD) derivatives with specific attention to the seminal vesicles, vas deferens, ureter, and kidneys. This is followed by a discussion of the history of the laparoscopic approach to WD derivative anomalies. Finally, we present two cases to describe technical considerations when managing these anomalies when encountered during robotic-assisted radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: The University of Chicago Robotic Laparoscopic Radical Prostatectomy (RLRP) database was reviewed for cases where anomalies of WD derivatives were encountered. We describe how modifications in technique allowed for completion of the procedure without difficulty. MEASUREMENTS: None RESULTS AND LIMITATIONS: Of the 1230 RLRP procedures performed at our institution by three surgeons, only two cases (0.16%) have been noted to have a WD anomaly. These cases were able to be completed without difficulty by making simple modifications in technique. CONCLUSIONS: Although uncommon, it is important for the urologist to be familiar with the origin and surgical management of WD anomalies, particularly when detected incidentally during surgery. Simple modifications in technique allow for completion of RLRP without difficulty.

The University of Chicago technique of complete intracorporeal pediatric robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendicovesicostomy.

We present the University of Chicago technique for complete intracorporeal robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendicovesicostomy. The operative steps of the open procedure were replicated laparoscopically using robotic assistance. Initially, five transperitoneal laparoscopic ports are placed prior to docking the da Vinci S robotic system. A 20 cm ileal segment is isolated, and the gastrointestinal anastomosis is performed in an end-to-end fashion using intracorporeal suturing. The appendix is anastomosed to the right posterior wall of the bladder over an 8F feeding tube in an extravesical fashion. Then, the bladder is incised in a coronal plane, and the simple detubularized ileal on-lay patch is anastomosed to the posterior and anterior walls of the bladder. A suprapubic catheter and pelvic drain are placed. Finally, the Mitrofanoff stoma is then fashioned. Cystography is done at 4 weeks postoperatively. This report suggests that robotic-assisted ileocystoplasty and appendicovesicostomy is feasible. A reasonable outcome with early recovery, resumption of normal activities, and excellent cosmesis can be achieved in select patients. A large case series, however, is necessary to determine whether a robotic-assisted approach provides any significant advantages over conventional open procedures.