Sujeet S. Acharya

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

Study Type – Therapy (case series) Level of Evidence 4

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.

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.