Radical Nephrectomy For Localized Renal Cell Carcinoma Research Articles

Impact of perioperative blood transfusion on oncologic outcomes in patients with nonmetastatic renal cell carcinoma treated with curative nephrectomy: A retrospective analysis of a large, single-institutional cohort.

PurposeTo evaluate the impact of perioperative blood transfusion (PBT) on oncologic outcomes after surgery in patients with nonmetastatic renal cell carcinoma (RCC).Materials and MethodsThis retrospective review included 2,329 patients who underwent partial or radical nephrectomy for localized RCC in a single institution from 2000 to 2014. PBT was defined as transfusion of allogeneic packed red blood cells (pRBCs) during nephrectomy or within the preoperative or postoperative hospitalization period. Oncologic outcomes of interest were recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS).ResultsPBT was performed in 275 patients (11.8%). In the multivariable logistic regression analysis, symptomatic presentation, advanced age at surgery, higher preoperative serum creatinine, and lower preoperative hemoglobin were independent preoperative risk factors for PBT (all p<0.05). Kaplan–Meier plots revealed that transfused patients showed poorer 5-year RFS (65.1% vs. 91.2%, p<0.001), OS (71.4% vs. 92.8%, p<0.001), and CSS (74.0% vs. 95.5%, p<0.001) than nontransfused patients. However, in the multivariable Cox regression analyses, PBT was not significantly associated with RFS, OS, or CSS. In multivariable analyses involving transfused patients only (n=275), an higher number of pRBC units was an independent predictor of worse OS (hazard ratio [HR], 1.043; 95% confidence interval [CI], 1.008–1.078; p=0.016) and CSS (HR, 1.066; 95% CI, 1.033–1.100; p<0.001).ConclusionsThe results of this study are inconclusive in that the influence of PBT on survival outcomes could not be determined in the multivariate analysis. However, increasing pRBC units in transfused patients might be a concern in light of worse OS and CSS. Therefore, efforts to limit PBT overuse seem necessary to improve postoperative survival in patients with RCC.

Prospective randomized controlled trial of conventional laparoscopic versus laparoendoscopic single-site radical nephrectomy for localized renal cell carcinoma: a preliminary report regarding quality of life.

The safety and efficacy of laparoendoscopic single-site surgery (LESS) for renal cell carcinoma (RCC) have not been clearly demonstrated. We aimed to present preliminary data from a prospective randomized controlled trial of LESS versus conventional laparoscopic radical nephrectomy for localized RCC. Patients with cT1-2 RCC were randomized to LESS (n = 17) or conventional laparoscopy (n = 18) group. The short-term outcome measures assessed were perioperative morbidity, postoperative pain, and quality of recovery as determined using QoR-40. No significant differences were observed between the LESS and conventional laparoscopy groups with respect to operative time (143.5 vs. 126.1 min, p = 0.218), blood loss (143.6 vs. 118.2 ml, p = 0.121), hospital stay (3.8 vs. 3.1 day s, p = 0.170), analgesic requirements (63.2 vs. 60.0 mg, p = 0.956), and complication rates (26.7 vs. 22.2 %, p = 0.767). However, postoperative quality of recovery was better in the LESS group (176.4 vs. 152.6, p = 0.005). Furthermore, quality of recovery, as measured using the QoR-40 dimensions of emotional state (39.9 vs. 34.0, p = 0.003), physical comfort (51.9 vs. 46.7, p = 0.034), psychological support (32.2 vs. 25.8, p = 0.003), and physical independence (20.7 vs. 17.5, p = 0.047), but not pain (31.8 vs. 29.6, p = 0.259), was significantly better in the LESS group. The preliminary results from this prospective trial suggest that LESS could be a safe and effective treatment option for localized RCC with equivalent surgical outcomes and improved postoperative quality of recovery compared with conventional laparoscopic surgery.

Expression of epithelial–mesenchymal transition markers in renal cell carcinoma: impact on prognostic outcomes in patients undergoing radical nephrectomy

What's known on the subject? and What does the study add? There have been few studies evaluating the prognostic value of epithelial-mesenchymal transition markers in renal cell carcinoma (RCC); therefore, the significance of these markers in the prognosis of patients with RCC, particularly that in those with localized disease, remains largely unknown. Consideration of the expression levels of potential epithelial-mesenchymal transition markers, particularly clusterin and Twist in addition to conventional prognostic parameters, would contribute to the prediction of disease recurrence after radical nephrectomy for localized renal cell carcinoma. • To evaluate the expression of multiple molecular markers involved in the process of epithelial-mesenchymal transition (EMT) in renal cell carcinoma (RCC) with the aim of clarifying the prognostic significance of these markers in patients undergoing radical nephrectomy. • The expression levels of 11 EMT markers, including E-cadherin, N-cadherin, β-catenin, γ-catenin, clusterin, Slug, Snail, Twist, vimentin, ZEB1 and ZEB2, in radical nephrectomy specimens from 122 patients with clinically localized RCC were measured by immunohistochemical staining. • In this series, disease recurrence occurred in 39 (32.0%) patients, with a 5-year recurrence-free survival rate of 64.4%. • Univariate analysis identified expression levels of E-cadherin, clusterin, Twist and vimentin, in addition to C-reactive protein (CRP) level, pathological stage and microvascular invasion, as significant predictors for disease recurrence. • Of these, expression levels of clusterin and Twist, CRP levels and microvascular invasion appeared to be independently related to disease recurrence on multivariate analysis. • There were significant differences in recurrence-free survival according to positive numbers of these four independent factors: disease recurrence occurred in two of 26 patients negative for any risk factor (7.7%), 23 of 73 patients positive for one or two risk factors (31.5%) and 14 of 23 patients positive for three or four risk factors (60.9%). • Consideration of the expression levels of potential EMT markers, particularly clusterin and Twist, in RCC specimens, in addition to conventional prognostic parameters, contributes to the accurate prediction of disease recurrence after radical nephrectomy for localized RCC.

Tongue metastasis as an initial manifestation of metastasis in renal cell carcinoma: A case report

Renal cell carcinoma (RCC) has unpredictable and diverse behavior. The classic triad of hematuria, loin pain and abdominal mass is uncommon. About 25 - 30% of patients are found to have metastases at the time of diagnosis. Bones, lungs, liver and brain are the frequent sites of metastases. RCC with metastasis to the oral cavity is rarest manifestation. We report a case of 35 years old male who underwent radical nephrectomy for localized RCC six years back, now presented with mass in the base of tongue which was suspected as carcinoma of tongue; subsequently was confirmed as metastatic RCC following excisional biopsy and was treated with intra-oral electron radiation therapy.

Learning Curve Analysis for Laparoendoscopic Single-Site Radical Nephrectomy

Little data are available on the learning curve for laparoendoscopic single-site (LESS) surgery. We aimed to evaluate the learning curve for LESS radical nephrectomy for localized renal-cell carcinoma (RCC). Data from the first 50 consecutive patients who underwent LESS radical nephrectomy were reviewed for evaluation of the learning curve. The surgical procedure was broken down into its three essential components (medial retraction of colon, hilar dissection, and kidney mobilization) through a video review, and each operative time was separately recorded for learning curve analysis. Patient demographic data, variable surgical outcomes, and pathologic outcomes were analyzed. Overall learning curve for LESS radical nephrectomy was evaluated, as well as individual learning curves for three essential steps of LESS radical nephrectomy. Operative time gradually decreased in about the first 15 cases and remained stable in the next 35 cases. The rate of perioperative complications did not differ significantly between groups, although it was higher in cases 1 to 15 and 16 to 30 than in cases 30 to 50 (20% vs 20% vs 0%). Surgeon experience regarding LESS was significantly correlated with time for medial retraction of colon (r=-0.502, P<0.001) and time for kidney mobilization (r=-0.457, P=0.001), but not with time for hilar dissection (r=-0.351, P=0.097). LESS radical nephrectomy for localized RCC is a safe and effective procedure needing a short learning curve for achievement of satisfying surgical outcomes in the hands of an experienced laparoscopic surgeon. Kidney mobilization appeared to be the step most affected by the learning curve in the early stage of LESS radical nephrectomy.

1660 CRP-BASED CLASSIFICATION OF LOCALIZED RENAL CELL CARCINOMA PATIENTS INTO LOW, INTERMEDIATE, AND HIGH RISK OF MORTALITY

INTRODUCTION AND OBJECTIVES: Approximately 30% of patients undergoing nephrectomy for localized Renal Cell Carcinoma (RCC) develop postoperative metastases. Preoperative C-reactive protein (CRP) is a robust predictor of outcomes. However, CRP cut-offs for Low, Intermediate, and High Risk groups have not been rationally derived. METHODS: 173 patients who underwent radical nephrectomy for localized RCC had CRP measured preoperatively. Receiver Operating Characteristics (ROC) curves were constructed to assess the potential of preoperative CRP to predict overall survival. ROC curves were used to determine the Area Under the Curve (AUC) and relative sensitivity and specificity of cut-offs. Based on these cut-offs, patients were categorized into Low, Intermediate, and High Risk groups. Kaplan-Meier survival curves were constructed to assess the impact of different cut-offs on overall survival. RESULTS: Preoperative CRP exhibited an AUC (95% CI) of 0.815 (0.718–0.911) (p 0.001). Three potential low risk (2.0, 3.0, and 4.0 mg/L) and three potential high risk (10.0, 15.0, and 25.0 mg/L) cut-offs were studied (Figure 1). The cut-offs 4.0 mg/L and 10.0 mg/L were the most discriminating based on population size and death frequency. Based on these cut-offs, patients were stratified into three categories: Low Risk (CRP: 4.0 mg/L), Intermediate Risk (CRP: 4.1–10.0 mg/L), and High Risk (CRP: 10.0 mg/L) Median (95% CI) survival for Low, Intermediate, and High Risk patients was 43.4 (42.2– 44.6) months, 41.8 (38.6–45.1) months, and 31.4 (39.8–43.4) months, respectively. K-M curves showed significant difference in survival among stratifications (Figure 2). Log-rank p-values were calculated comparing: Low Risk versus High Risk (p 0.001), Low Risk versus Intermediate Risk (p 0.06), Intermediate-Risk versus High Risk (p 0.009). CONCLUSIONS: Preoperative CRP is a robust molecular marker for predicting outcomes in patients undergoing potentially curative nephrectomy for localized RCC. This tool’s use can be increased through trinary categorization. Clinicians may wish consider the outcome differences among these distinct groups in preoperative counseling, postoperative management, and clinical guidelines. Source of Funding: None

1662 EXPRESSION OF POTENTIAL MOLECULAR MARKERS IN RENAL CELL CARCINOMA: IMPACT ON CLINICOPATHOLOGICAL OUTCOMES IN PATIENTS UNDERGOING RADICAL NEPHRECTOMY

INTRODUCTION AND OBJECTIVES: Renal cell carcinoma (RCC) has been shown to be characterized by the unique biological feature as well as the heterogenous genetic background, suggesting the limitations for predicting postoperative outcomes in patients with localized RCC using conventional parameters alone. The objective of this study was to evaluate the expression levels of multiple potential molecular markers in RCC to clarify the significance of these markers as prognostic predictors in patients undergoing radical nephrectomy. METHODS: This study included 153 patients with clinically organ-confined RCC undergoing radical nephrectomy. Expression levels of 12 proteins, including Aurora-A, Bcl-2, Bcl-xL, clusterin, heat shock protein 27 (HSP27), HSP70, HSP90, Ki-67, matrix metalloproteinase (MMP)-2, MMP-9, p53 and vascular endothelial growth factor, in radical nephrectomy specimens obtained from these 153 patients were measured by immunohistochemical staining. RESULTS: Of the 12 markers, clusterin, HSP27, Ki-67, MMP-2 and MMP-9 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these five markers as significant predictors for disease recurrence as well, while mode of presentation, pathological stage, grade and microvascular invasion were also significant. Of these significant factors, Ki-67 expression, pathological stage and microvascular invasion appeared to be independently related to disease recurrence. Furthermore, there were significant differences in recurrence-free survival according to positive numbers of these three independent factors; that is, disease recurrence occurred in 4 of 56 patients who were negative for risk factor (7.1%), 17 of 71 positive for a single risk factor (23.9%), and 20 of 26 positive for 2 or 3 risk factors (76.9%). CONCLUSIONS: These findings suggest that consideration of expression levels of potential molecular markers in RCC specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of disease recurrence following radical nephrectomy for localized RCC. Moreover, combined evaluation of Ki-67 expression, pathological stage and microvascular invasion would be particularly useful for further refinement of the system in predicting prognostic outcome following radical nephrectomy for patients with RCC.

Activated extracellular signal‐regulated kinase is an independent prognostic factor in clinically confined renal cell carcinoma

Extracellular signal-regulated kinase (ERK) promotes proliferation, metastasis, and poor survival in cancers of the breast, lung, and liver. Advanced localized renal cell carcinoma (RCC) is extraordinarily treatment resistant and has high recurrence rates despite surgery. Limited data exist regarding the prognostic significance of activated (phosphorylated) ERK in RCC. The authors hypothesized that activated ERK (pERK) promotes disease progression and metastasis in localized RCC and may be of value as a biomarker to predict disease recurrence. The expression profile of pERK was examined by immunocytochemistry using a tissue microarray constructed from 174 drug treatment-naive patients who had undergone radical nephrectomy for localized RCC. Levels of tumor-cell specific pERK were scored and correlated with clinicopathologic parameters of RCC and disease-free survival. Immunostaining for pERK was present in 36% of all RCCs, with a predominance found in the clear cell histologic subtype. High expression was associated with increased tumor size, increased TNM stage, and vascular invasion. Patients with pERK-positive tumors had a mean disease-free survival of 4.19 years, compared with 6.38 years for patients with pERK-negative tumors (P<.001). Cox regression models revealed pERK to be a significant independent predictor of disease-free survival, with a hazards score of 2.9 (P<.001), a value similar to tumor grade (hazards ratio, 3.01; P<.001). Expression of pERK is an independent prognostic factor in RCC that is associated with advanced and aggressive pathologic features of renal tumors and predicts the onset of metastasis in patients with localized disease.

A prospective comparison of laparoscopic and robotic radical nephrectomy for T1-2N0M0 renal cell carcinoma

We prospectively evaluated the safety, feasibility, and efficiency of robotic radical nephrectomy (RRN) for localized renal tumors (T1-2N0M0) and compared this with laparoscopic radical nephrectomy (LRN). Between October 2006 to August 2007, a prospective data analysis of 15 cases of renal cell carcinoma (RCC) stage T1-2N0M0, undergoing RRN was done. These patients were compared with a contemporary cohort of 15 patients of RCC with clinical stage T1-2N0M0, undergoing LRN. To keep comparison robust, all cases were performed by a single surgeon. Demographic, intra-operative, post-operative outcomes, pathological characteristics and follow-up data of the two groups were recorded and analyzed statistically. Patients in group A (RRN) experienced significantly (P = 0.001) long operating time than group B (LRN). However, mean estimated blood loss, intra-operative and post-operative complications, blood transfusion rate, analgesic requirement, hospital stay and convalescence were comparable in two groups (P < 0.05). There was one conversion to open surgery in group A, and none in group B. The mean follow-up was comparable in two groups (8.3 and 9.1 months, respectively, in group A and B, P = 0.09). There were no local, port-site or distal recurrences in either group. Robotic radical nephrectomy is a safe, feasible and effective for performing radical nephrectomy for localized RCC. Both groups (RRN and LRN) had comparable intra-operative, peri-operative, post-operative and oncological outcomes except for longer operating time with increased cost for RRN. In this comparative study, there were no outstanding benefits of RRN observed over LRN for localized RCC.

Increased preoperative serum C‐reactive protein level predicts a poor prognosis in patients with localized renal cell carcinoma

To evaluate the value of the preoperative serum C-reactive protein (CRP) level in the prognosis of patients with localized renal cell carcinoma (RCC). The study comprised 101 patients who had a radical nephrectomy for localized RCC (pT1-3N0M0). An elevated CRP was defined as >0.5 mg/dL before surgery. Survival rates for each variant were calculated using the Kaplan-Meier method, with the difference between survival curves evaluated using the log-rank test. Multivariate analysis was by Cox proportional hazard model; for all analyses the difference was considered significant when P < 0.05. The median (range) follow-up was 55 (2-187) months; 26 patients (26%) had high CRP levels, and 12 (46%) of these and three (4.0%) of the remaining 75 died from disease. The 5- and 10-year disease-specific survival rates (75% and 30%, respectively) in patients with high CRP levels were significantly worse than those in patients with normal CRP levels (both 93%, P < 0.001). In other variants, preoperative haemoglobin concentration, pathological stage, grade, histological type and microvascular tumour invasion were also related to disease-specific survival. By the Cox proportional hazards model, pathological stage and an elevated CRP were the most important prognostic factors for disease-specific survival in patients with localized RCC (P = 0.008 and 0.012, respectively). The preoperative CRP level was associated with poor survival in patients with localized RCC.

Solitary breast mass as initial presentation of clinically silent metastatic renal cell carcinoma

Metastasis to the breast from extramammary tumors is rare. Breast metastases of renal cell carcinoma (RCC) origin have been described in sporadic case reports. We present a patient with a solitary breast mass representing the manifestation of clinically silent, metastatic RCC. A 76-year-old female was 12 years prior removed from radical nephrectomy for localized RCC. Her new breast mass was identified on physical examination. Pathology of the resected mass was diagnostic of metastatic RCC and subsequent imaging studies demonstrated a 1.9 cm renal mass in her solitary kidney. The patient elected subcutaneous Interleukin-2 immunotherapy as primary treatment for her recurrent RCC.

Proposal for revision of the TNM classification system for renal cell carcinoma

The current study defined an optimal tumor size breakpoint to stratify localized renal cell carcinoma (RCC) into groups with significantly different cancer-related outcomes and proposed a revision of the TNM classification system. The authors analyzed the data from 1138 patients who had undergone partial or radical nephrectomy for localized RCC at 7 European urologic centers. The optimal pathologic size breakpoint was calculated using the martingale residuals from a Cox proportional hazards regression model. The mean follow-up time was 87 months. The scatterplot of tumor size versus expected risk of death per patient suggested that an interval of 5-6 cm was appropriate. A total of 720 (63.3%) and 418 (36.7%) patients had tumors measuring < or = 5.5-cm and tumors measuring > 5.5-cm, respectively. Significant cancer-specific survival differences between the two groups of patients were reported in the series by all the centers participating in the study. On univariate analysis, the other variables found to be associated with cancer-specific survival were the patient's age, symptomatic tumor presentation, and the Fuhrman nuclear grade. On multivariate analysis, the pathologic stage of the primary tumor defined according to the 5.5-cm breakpoint was found to be an independent predictor of cancer-specific survival, as well as age, mode of presentation, and nuclear grade. According to the multivariate analysis, the authors clustered patients into 3 groups with statistically significant outcome differences: 1) patients with < or = 5.5-cm incidentally detected RCC; 2) patients with < or = 5.5-cm symptomatic RCC; and 3) patients with > 5.5-cm RCC. This cancer-related outcome stratification was valid regardless of the patient's age. The 5.5-cm breakpoint was found to be the optimal tumor size breakpoint with which to stratify patients with organ-confined RCC. The study supported the upgrade of the TNM classification system according to this breakpoint.

Laparoscopic Radical Nephrectomy: Long-Term Outcomes

Although more than a decade of experience with laparoscopic radical nephrectomy indicates it is an alternative to open surgery for localized renal-cell carcinoma (RCC), the long-term oncologic effectiveness of this procedure remains to be established. A thorough MEDLINE and PubMed literature research on long-term outcomes of laparoscopic radical nephrectomy was performed, and all pertinent articles were reviewed in detail. This review was formulated on the current cancer indication, the oncologic basis, the oncologic efficacy, and the longterm oncologic effectiveness of the procedure, including laparoscopic cytoreductive nephrectomy, with regard to metastasis, port-site tumor recurrence, and the relation to laparoscopic partial nephrectomy. Furthermore, the authors' previous report on the intermediate-term efficacy of laparoscopic radical nephrectomy was updated. With increasing experience, the indications for laparoscopic radical nephrectomy continue to expand. There were many reports of intermediate-term, two reports of long-term, and our up-to-date outcomes analyzing the management of localized RCC that showed effective cancer control with no statistically significant difference between laparoscopic and open radical nephrectomy in the true 5- and 10-year survival analysis. Long-term data, critical in the evaluation of any treatment for cancer, are currently available with respect to laparoscopic radical nephrectomy for localized RCC.