Bilateral Synchronous Sporadic Renal Cell Carcinoma: Retroperitoneoscopic Strategies and Intermediate Outcomes of 60 Patients

<div><p>Objective</p><p>To evaluate the presentation, management, pathology, and functional and oncological outcomes of patients undergoing retroperitoneoscopic treatment of bilateral synchronous sporadic RCC at our institution.</p><p>Methods</p><p>We retrospectively evaluated the records of 60 patients with bilateral synchronous sporadic RCC who underwent retroperitoneoscopic treatment at the General Hospital of People's Liberation Army from 2008 to 2014. The estimated glomerular filtration rate was calculated and compared among different surgical procedures. The overall survival and recurrence free survival were assessed based on information from recent follow-up.</p><p>Results</p><p>Fifty-six patients underwent bilateral retroperitoneoscopic surgeries in staged procedures, and four patients underwent bilateral retroperitoneoscopic surgeries in simultaneous procedures. Among the former group of patients, 34 underwent bilateral partial nephrectomy, 12 underwent radical nephrectomy followed by partial nephrectomy, and 10 underwent partial nephrectomy followed by radical nephrectomy. Bilateral partial nephrectomy can better preserve renal function (p = 0.040) and the sequence of partial nephrectomy and radical nephrectomy did not affect functional outcomes (p = 0.790). One patient undergoing simultaneous procedures developed acute renal failure and required temporary hemodialysis. At 3 and 5 years, overall survival rates were 93.0% and 89.4%, and recurrence free survival rates were 90.5% and 81.6%. High nuclear grade (p = 0.014) was related to disease recurrence.</p><p>Conclusions</p><p>Staged bilateral partial nephrectomy was efficient in preserving renal function. The survival of patients with bilateral synchronous sporadic renal tumors was similar to that of patients with unilateral nonmetastatic tumors. Nuclear grade was an independent prognostic factor of disease recurrence.</p></div

Renal functional changes for different surgical procedures.

<p>The patients of RPN-RPN, RRN-RPN and RPN-RRN groups exhibited 22%, 30% and 17% decrease rates in eGFR undergoing the first operation, and 32%, 29%, and 45% undergoing the second operation, respectively.</p

Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumors treated with different surgical procedures and sequences.

<p>Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumors treated with different surgical procedures and sequences.</p

Univariate and multivariate cox regression analysis predicting disease recurrence in patients treated with bilateral retroperitoneal laparoscopic surgeries.

<p>Univariate and multivariate cox regression analysis predicting disease recurrence in patients treated with bilateral retroperitoneal laparoscopic surgeries.</p

Patients, tumors and subsequent clinical behavior.

<p>Patients, tumors and subsequent clinical behavior.</p

Renal functional changes of stage procedure^*.

<p>Renal functional changes of stage procedure^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154578#t003fn002" target="_blank">*</a>}.</p

MicroRNA-19a and microRNA-19b promote the malignancy of clear cell renal cell carcinoma through targeting the tumor suppressor RhoB

<div><p>Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, which shows high aggressiveness and lacks biomarkers. RhoB acts as a tumor suppressor that inhibits the progression of ccRCC. In the present study, we examined the effects of oncogenic microRNAs, miR-19a and miR-19b, on RhoB expression in ccRCC cells. The results showed that both miR-19a and miR-19b could directly target the 3′untranslated region (3’UTR) of RhoB, resulting in the reduced expression of RhoB. With RT-PCR analysis, we detected the increased expression of miR-19a and miR-19b in ccRCC tissues compared to adjacent non-tumor renal tissues. These data also demonstrated an exclusive negative correlation between miR-19a/19b and RhoB expression in ccRCC specimens and cell lines. In addition, the knockdown of RhoB or overexpression of miR-19a and miR-19b in ccRCC cells could promote cell proliferation, migration and invasion. These data demonstrate the direct roles of miR-19a and miR-19b on the repression of RhoB and its consequences on tumorigenesis, cancer cell proliferation and invasiveness. These results suggest the potential clinical impact of miR-19a and miR-19b as molecular targets for ccRCC.</p></div

MiR-19a and miR-19b inhibitors reduce cell migration and invasiveness, and inhibit cell proliferation.

<p>(A) Representative images showing that the transfection of miR-19a and miR-19b inhibitors decreases the migration of 786-O cells by wound healing assay (Left); quantification of relative migration at 12 and 24 h (Right). (B) Representative images and quantification of relative migration, showing that the transfection of miR-19a and miR-19b inhibitors reduces the invasiveness of 786-O cells by transwell assay. The migratory activities of 786-O cells transfected with control oligo were was included as a negative inhibitor control. (C) The proliferation potential of 786-O cells transfected with miR-19a and miR-19b inhibitors or control oligo was determined by the MTS Assay. The data are representative of three independent experiments. *Significant differences from control oligo-transfected cells (P<0.05).</p

Primer sequences used in the present study.

<p>Primer sequences used in the present study.</p

MiR-19a and miR-19b inhibitors induce cell apoptosis.

<p>(A) Flow cytometry results of Annexin-V5 analysis in 786-O cells transfected with miR-19a and miR-19b inhibitors. An inhibitor control was included as a negative control. Graphs showing changes of the apoptotic percentage of the cells (left); quantification of relative apoptosis (right). The data represent the means ± S.D. from three independent experiments performed in triplicate. *Significant differences from control oligo-transfected cells (P<0.05) (B) Western blot results showing the effect of miR-19a and miR-19b inhibitors on the expression of cleaved caspase-9 in 786-O cells. (C) Potential mechanism showing the effect of the negative regulation of RhoB by miR-19a/b on the proliferation, migration, invasion and apoptosis of ccRCC.</p