Profiling microRNA from nephrectomy and biopsy specimens: predictors of progression and survival in clear cell renal cell carcinoma.

OBJECTIVE: To identify microRNA (miRNA) characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer-specific survival (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue. MATERIALS AND METHODS: RNA was isolated from nephrectomy and kidney biopsy specimens (n = 156 and n = 46, respectively). Samples were grouped: benign, non-progressive, and progressive ccRCC. MiRNAs were profiled by microarray and validated by quantitative reverse transcription-polymerase chain reaction. Biomarker signatures were developed to predict cancer status in nephrectomy and biopsy specimens. CSS was examined using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Microarray analysis revealed 20 differentially expressed miRNAs comparing non-progressive with progressive tumours. A biomarker signature validated in nephrectomy specimens had a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and ccRCC specimens. A second signature differentiated non-progressive vs progressive ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b-5p, and -223-3p were associated with CSS. CONCLUSION: This study identified miRNAs differentially expressed in ccRCC samples; as well as those correlating with CSS. Biomarkers identified in this study have the potential to identify patients who are likely to have progressive ccRCC, and although preliminary, these results may aid in differentiating aggressive and indolent ccRCC based on biopsy specimens.

Endovascular Removal of Intracardiac Thrombus Prior to Radical Nephrectomy and Inferior Vena Cava Thrombectomy.

We report a case of a 54-year-old patient with a T3c renal mass with intracardiac extension of the thrombus to the level of the pulmonary valve. The patient was not a candidate for cardiopulmonary bypass due to recent pulmonary embolism. Under transesophageal echocardiogram guidance, the intracardiac thrombus was removed percutaneously via transvenous mechanical thrombectomy. The patient was effectively downstaged to T3b and underwent successful radical nephrectomy and inferior vena cava thrombectomy without the use of cardiopulmonary bypass.

Urethral Reconstruction with Rectal Mucosa Graft Onlay: A Novel, Minimally Invasive Technique.

PURPOSE: Alternative grafts are needed for patients who are not suitable candidates for oral mucosa graft harvest or who have a paucity of oral mucosa graft available for reconstruction. Circumferential colonic mucosal grafts have demonstrated feasibility for urethral reconstruction, although sigmoid resection has been required for graft retrieval. We report the feasibility and short-term outcomes of urethral reconstruction using a rectal mucosa graft harvested by a novel, minimally invasive, transanal endoscopic microsurgical technique. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent transanal endoscopic microsurgical rectal mucosa graft harvest and onlay urethroplasty since the technique was first implemented in 2013. Graft failure was defined as inability to pass a 16Fr cystoscope in the grafted urethra. RESULTS: All 4 strictures were bulbopendulous with a median length of 13.5 cm (range 10 to 21). Median followup was 18 months (range 12 to 28). Stricture etiology was lichen sclerosus in 3 patients and failed hypospadias interventions in 1. Three patients had undergone at least 1 prior urethroplasty. In 1 patient stricture recurred in the graft 10 months following reconstruction. There were no colorectal complications. CONCLUSIONS: To our knowledge this is the first study demonstrating urethral reconstruction using a rectal mucosa graft harvested by the transanal endoscopic microsurgical technique. Initial data revealed that this technique is feasible and safe, and minimizes graft harvest morbidity. Transanal endoscopic microsurgical harvest of a rectal mucosa graft may provide an alternative graft material for patients with long segment urethral strictures who are not candidates for oral mucosa graft harvest. Further experience and longer followup are needed to validate these findings.

Urethroplasty for high risk, long segment urethral strictures with ventral buccal mucosa graft and gracilis muscle flap.

PURPOSE: Long segment urethral strictures with a compromised graft bed and poor vascular supply are unfit for standard repair and at high risk for recurrence. We assessed the success of urethral reconstruction in these patients with a ventral buccal mucosa graft and gracilis muscle flap. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,039 patients who underwent urethroplasty at Lahey Hospital and Medical Center between 1999 and 2014. We identified 20 patients who underwent urethroplasty with a ventral buccal mucosa graft and a gracilis muscle flap graft bed. Stricture recurrence was defined as the inability to pass a 16Fr cystoscope. RESULTS: Mean stricture length was 8.2 cm (range 3.5 to 15). Strictures were located in the posterior urethra with or without involvement of the bulbar urethra in 50% of cases, and in the bulbomembranous urethra in 35%, the bulbar urethra in 10% and the proximal pendulous urethra in 5%. Stricture etiology was radiation therapy in 45% of cases, followed by an idiopathic cause in 20%, trauma in 15%, prostatectomy in 10%, and hypospadias failure and transurethral surgery in 5% each. Nine patients (45%) were previously treated with urethroplasty and 3 (15%) previously underwent UroLume® stent placement. Urethral reconstruction was successful in 16 cases (80%) at a mean followup of 40 months. One of the patients in whom treatment failed had an ileal loop, 2 had a suprapubic tube and urethral dilatation had been done in 1. Mean time to recurrence was 10 months (range 2 to 17). Postoperatively 5 patients (25%) had incontinence requiring an artificial urinary sphincter. CONCLUSIONS: Urethroplasty for high risk, long segment urethral strictures can be successfully performed with a ventral buccal mucosa graft and a gracilis muscle flap, avoiding urinary diversion in most patients.

A systematic review of the quality of evidence of ablative therapy for small renal masses.

PURPOSE: We critically assessed the methodological and reporting quality of published studies of ablative techniques for small renal masses. MATERIALS AND METHODS: We performed a systematic PubMed® and EMBASE® literature search from January 1966 to March 2010 to identify all full text, original research publications on ablative therapy for renal masses. Six reviewers working independently in 3 teams performed duplicate data abstraction using Strengthening the Reporting of Observational Studies in Epidemiology criteria, which were pilot tested in a separate sample. RESULTS: A total of 117 original research publications published in a 15-year period (1995 to 2009) met eligibility criteria. No randomized, controlled trials were identified. All studies were observational and 88.9% had 1 arm with no comparison group. Median sample size was 18 patients (IQR 5.5, 40.0) and 53.8% of studies included 20 or fewer patients. Median followup was 14.0 months (IQR 8.0, 23.8) and only 19.7% of studies had an average followup of greater than 24 months. Of the studies 20.5% mentioned the number of operators involved and only 6.0% provided information on their experience level. Of the studies 66.7% addressed the recurrence rate. Disease specific and overall survival was reported in only 15.4% and 16.2% of studies, respectively. CONCLUSIONS: The published literature on the therapeutic efficacy of ablative therapy for renal masses is largely limited to uncontrolled, 1-arm observational studies. In the absence of higher quality evidence ablative therapy outside research studies should be limited to select patients who are not candidates for surgical intervention.