MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype.

The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3-T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease.

Robotic unclamped "minimal-margin" partial nephrectomy: ongoing refinement of the anatomic zero-ischemia concept.

BACKGROUND: Anatomic partial nephrectomy (PN) techniques aim to decrease or eliminate global renal ischemia. OBJECTIVE: To report the technical feasibility of completely unclamped "minimal-margin" robotic PN. We also illustrate the stepwise evolution of anatomic PN surgery with related outcomes data. DESIGN, SETTING, AND PARTICIPANTS: This study was a retrospective analysis of 179 contemporary patients undergoing anatomic PN at a tertiary academic institution between October 2009 and February 2013. Consecutive consented patients were grouped into three cohorts: group 1, with superselective clamping and developmental-curve experience (n = 70); group 2, with superselective clamping and mature experience (n = 60); and group 3, which had completely unclamped, minimal-margin PN (n = 49). SURGICAL PROCEDURE: Patients in groups 1 and 2 underwent superselective tumor-specific devascularization, whereas patients in group 3 underwent completely unclamped minimal-margin PN adjacent to the tumor edge, a technique that takes advantage of the radially oriented intrarenal architecture and anatomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes assessed the technical feasibility of robotic, completely unclamped, minimal-margin PN; short-term changes in estimated glomerular filtration rate (eGFR); and development of new-onset chronic kidney disease (CKD) stage >3. Secondary outcome measures included perioperative variables, 30-d complications, and histopathologic outcomes. RESULTS AND LIMITATIONS: Demographic data were similar among groups. For similarly sized tumors (p = 0.13), percentage of kidney preserved was greater (p = 0.047) and margin width was narrower (p = 0.0004) in group 3. In addition, group 3 had less blood loss (200, 225, and 150ml; p = 0.04), lower transfusion rates (21%, 23%, and 4%; p = 0.008), and shorter hospital stay (p = 0.006), whereas operative time and 30-d complication rates were similar. At 1-mo postoperatively, median percentage reduction in eGFR was similar (7.6%, 0%, and 3.0%; p = 0.53); however, new-onset CKD stage >3 occurred less frequently in group 3 (23%, 10%, and 2%; p = 0.003). Study limitations included retrospective analysis, small sample size, and short follow-up. CONCLUSIONS: We developed an anatomically based technique of robotic, unclamped, minimal-margin PN. This evolution from selective clamped to unclamped PN may further optimize functional outcomes but requires external validation and longer follow-up. PATIENT SUMMARY: The technical evolution of partial nephrectomy surgery is aimed at eliminating global renal damage from the cessation of blood flow. An unclamped minimal-margin technique is described and may offer renal functional advantage but requires long-term follow-up and validation at other institutions.

Flank muscle volume changes after open and laparoscopic partial nephrectomy.

PURPOSE: To determine the occurrence of flank symptoms, flank muscle atrophy, bulge, and hernia formation after open and laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: Our prospective Institutional Review Board-approved database was queried to identify 50 consecutive patients who were treated with open partial nephrectomy (OPN) and 50 consecutive patients who were treated with LPN between September 2006 and May 2008. Study patients had: Solitary clinical T1 renal tumor, preoperative and ≥6 month postoperative CT scan performed at our institution, and a confirmed renal-cell carcinoma on the final pathology report. Patients with previous abdominal surgery and neuromuscular disorders were excluded. Oncocare software was used to measure abdominal wall musculature on preoperative and postoperative CT scan. Bilateral flanks were compared for muscle volume, bulge, and hernia. Patients were administered a phone questionnaire to assess postoperative flank symptoms. RESULTS: No statistical significant difference was found in the demographics between the two groups. Median age (range) was 59.9 years (20.6-80.7) in the OPN group and 57.5 years (25-78) in the LPN group (P=0.89). Median (range) body mass index and American Society of Anesthesiologists scores were similar between the two groups. On CT scans, median percent variation (range) in abdominal wall muscle volume was significantly greater in the OPN group: -1.03% (-31.4-1.5) vs-0.39% (-5.2-1.8) (P=0.006). The median extent of flank bulge on CT scans (range) was also greater in the OPN group: 0.75 cm (-1.9-7.6) vs 0 cm (-2.7-2.8) (P=0.0004). The OPN group was also more symptomatic, including paresthesia 48% vs 8% (P=0.0053); numbness 44% vs 0% (P=0.002); and flank bulge 57% vs 12% (P=0.007). CONCLUSIONS: Minimally invasive partial nephrectomy has lesser deleterious impact on flank muscle volume compared with OPN with fewer symptoms of flank bulge, paresthesia, and numbness.

Does eliminating global renal ischemia during partial nephrectomy improve functional outcomes?

PURPOSE OF REVIEW: Presently, there is debate over what drives ultimate postoperative function after partial nephrectomy. Some argue that volume of preserved parenchyma and baseline renal function virtually exclusively drive functional outcomes. Others contend that global renal ischemic injury also matters. Herein, we critically review recent literature, with particular focus on emerging data of functional outcomes after ischemia-free partial nephrectomy. RECENT FINDINGS: Recent retrospective reports suggest the primacy of renal volume preservation and baseline renal function over ischemia time in impacting post-partial nephrectomy function. These studies rely on historical series when the technique of selective clamping was not available. Data from more contemporary series indicate superior functional outcomes when partial nephrectomy is performed without global ischemia, even after correcting for volume loss. Elimination of global ischemia is made possible through novel technical refinements, such as anatomical partial nephrectomy surgery. SUMMARY: Amount of kidney excised and ischemia time are inseparably interlinked; the larger/deeper the tumor, the longer the ischemia time. Post-partial nephrectomy kidney quantity and quality are surgically nonmodifiable; however, ischemia time is. Anatomical tumor-specific devascularization opens the door to more sophisticated partial nephrectomy surgery, wherein we can now tailor the technique to the individual tumor and patient.

Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder.

Removal of toxic substances from the blood depends on patent connections between the kidney, ureters and bladder that are established when the ureter is transposed from its original insertion site in the male genital tract to the bladder. This transposition is thought to occur as the trigone forms from the common nephric duct and incorporates into the bladder. Here we re-examine this model in the context of normal and abnormal development. We show that the common nephric duct does not differentiate into the trigone but instead undergoes apoptosis, a crucial step for ureter transposition controlled by vitamin A-induced signals from the primitive bladder. Ureter abnormalities occur in 1-2% of the human population and can cause obstruction and end-stage renal disease. These studies provide an explanation for ureter defects underlying some forms of obstruction in humans and redefine the current model of ureter maturation.