Early-stage Renal Cell Carcinoma Research Articles

Proton Stereotactic Body Radiotherapy as a Nephron-Sparing Approach for Patients with Localized Renal Cell Carcinoma: A Dosimetric Analysis

Radiotherapy for renal cell carcinoma (RCC) is limited by the radiosensitivity of both the kidney and nearby structures. Patients with compromised renal function are at further risk of kidney injury from the low-dose bath from VMAT-based SBRT. Our aim was to demonstrate the potential nephron-sparing dosimetry of pencil beam scanning (PBS) proton radiotherapy SBRT for early stage RCC. Three patients previously treated for pancreatic cancer were randomly selected. Spherical CTV contours were drawn to mimic renal tumors at 4 locations (superior and inferior poles, pelvis, and mid-posteriorly) in each kidney and 3 different sizes (1, 2, and 4 cm) per location. Dose prescription was 54 Gy in 3 fractions. Proton plans were robustly optimized to 3 mm. Photon plans had a 3 mm PTV expansion. 2-arc VMAT plans and orthogonal-pair proton plans were generated for every tumor. The subset of renal-pelvis and superior pole tumors additionally had oblique pair and single beam proton plans generated. DVHs for all plans were analyzed through custom software developed in-house. Ipsilateral kidney doses were calculated after subtracting the CTV. 216 treatment plans (72 photon and 144 proton) and corresponding DVHs were generated. The ipsilateral kidney V < 12 Gy was selected as our nephron-sparing metric. Single beam proton plans showed a mean 12.7% absolute improvement in V < 12 Gy, while orthogonal pair plans showed a 4.3% improvement (see table). Oblique-pair proton plans were in-between (data not shown). After accounting for location, the difference seen for orthogonal pair plans was only significant for mid-posterior tumors (mean 18.9% improvement in V < 12 Gy, p = 0.0002). However, mean improvement in V < 12 Gy was significant regardless of location for single-beam plans. Protons also yielded superior duodenum and small bowel dosimetry: Mean V20 Gy was 0.39 cc and 2.31 cc respectively for proton plans, vs. 1.54 cc and 5.54 cc respectively for photon plans. Proton beam angle and single vs. paired proton beams did not significantly alter dosimetry to OARs. Dosimetric parameters did not vary significantly based on laterality or size of the tumor. Other ROIs met dosimetric constraints regardless of treatment modality. PBS proton treatment planning demonstrates promise in the treatment of renal tumors and significantly improves nephron-sparing dosimetry. Notable improvements in dosimetric parameters for critical radiosensitive organs were seen compared to photons in this large treatment-plan analysis. Further analyses identifying optimal patient selection criteria will support future development of clinical protocols.Abstract 3663; Table 1Single Beam PBSOrthogonal Pair PBSCritical ROIsMean Ipsilateral Kidney V < 12 GyMean Ipsilateral Kidney V < 12 GyMean Duodenum V20 GyMean Small Bowel V20 GyProtons84.2 ± 15.4%75.8 ± 16.7%0.39 ± 1.59 cc2.31 ± 8.07 ccPhotons71.5 ± 19.7%71.5 ± 19.7%1.54 ± 5.51 cc5.54 ± 16.37 ccMean difference12.7%4.3%1.15 cc3.23 ccp0.00320.0480.0002910.000041 Open table in a new tab

Circulating miR-200a is a novel molecular biomarker for early-stage renal cell carcinoma

BackgroundCirculating microRNAs (miRNAs) have been recognized as novel molecular markers for renal cell carcinoma (RCC) diagnosis. However, the clinical impact of circulating miRNA has rarely been evaluated for the early detection of RCC. Moreover, miRNAs also play important roles in regulating RCC tumorigenesis. The aim of this study is to assess the serum signatures of the epithelial–mesenchymal transition (EMT)-related miRNA-200 family in RCC patients and evaluate their diagnostic usefulness for early-stage RCC, and further explore the functions of specifically altered miRNAs that regulate pathological genes during the RCC tumorigenesis.MethodsThe serum levels of three miR-200 miRNAs (miR-200a, miR-200b and miR-200c) were firstly measured in 26 RCC patients and 26 noncancer controls of the training phase using quantitative real-time polymerase chain reaction (RT-qPCR). Markedly dysregulated miRNAs in RCC patients were subsequently verified by RT-qPCR in an independent validation phase that consist of 73 patients and 73 controls. Differentially expressed miRNAs were further examined in RCC urine samples and corresponding controls. Additionally, the mechanisms underlying the altered miRNAs involved in RCC tumorigenesis were also elucidated.ResultsOf the three examined miRNAs, only miR-200a showed consistently decreased levels in serum of the RCC patients, especially in those with stage I disease, as compared with controls (P < 0.001). MiR-200a is also frequently downregulated in RCC urine samples. Mechanistic investigations revealed that E2F3, an oncogene with strong proliferative and cell cycle regulation potential, is a direct target gene of miR-200a in RCC. E2F3 protein levels in RCC tissues and cell lines were increased and inversely associated with miR-200a levels. Upregulation of miR-200a decreased the expression of E2F3, with consequent repressed RCC cell proliferation and induced cell cycle arrest at G0/G1 phase in vitro. In contrast, inhibition of miR-200a in RCC cells resulted in increased expression of E2F3 and enhanced cell proliferation, and promoted G1/S transition.ConclusionsSerum miR-200a has the potential to be served as a novel noninvasive auxiliary diagnostic biomarker for the early detection of RCC, and the identified novel molecular interaction between miR-200a and E2F3 may provide insights into novel therapies for RCC.

Renal cell carcinoma trends in Latvia: incidence, mortality, and survival rates. Population-based study.

IntroductionBaltic States including Latvia are reported as having one of the highest renal cell carcinoma (RCC) incidence and mortality rates in the world. However, data are often presented without stage-specific stratification, making assessment of the overall RCC diagnosis and survival trends challenging.Material and methodsWe collected data on all newly diagnosed RCC patients from the national population-based cancer registry between 1997 and 2016. We analyzed RCC incidence, mortality and survival trends using Joinpoint analysis. Kaplan-Meier analysis was performed for 5- and 10-year cancer specific survival rate calculations.ResultsThere were a total of 7893 patients with newly diagnosed RCC. The age standardized (AS) incidence rate (per 100,000) increased slightly from 8.9 in 1997 to 9.8 in 2016. There were no specific changes in the incidence rate trend. Detection of early stage RCC increased by 5.4% annually. The AS mortality rates (per 100,000) decreased from 4.9 in 1997 to 3.9 in 2016, however, it did not reach a statistically significant change. The mortality rates decreased significantly in females and in the age group of 60-69 years. The 5-year cancer specific survival (CSS) rate increased from 55.1% in 1997-2001 to 66.6% in years 2007–2011. The 10-year CSS rate increased from 49.1% in 1997–2001 to 56.5% in years 2002–2006.ConclusionsDuring the study period, RCC incidence rates increased and overall mortality rates did not change. Similar to the rest of the world, the incidence of RCC diagnosed at an earlier stage increased and 5- and 10-year survival rates improved.

Metastatic Renal Cell Carcinoma: The role of surgery in the treatment algorithm

Renal cell carcinoma (RCC) is a life threatening disease, the most lethal among urinary tract tumors. It accounts for about 2-3% of adult solid malignancies, with a reported worldwide annual increase of 1.5-5.5%. Surgical intervention is the primary treatment for early-stage RCC, however nephrectomy alone offers limited benefit in patients with metastatic disease, except for palliative reasons. The aim of this review is to study the role of surgical intervention in the treatment algorithm of metastatic renal cell carcinoma.

Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma

BackgroundPlasma glycosaminoglycan (GAG) measurements, when aggregated into diagnostic scores, accurately distinguish metastatic clear-cell renal cell carcinoma (RCC) from healthy samples and correlate with prognosis. However, it is unknown if GAG scores can detect RCC in earlier stages or if they correlate with prognosis after surgery. ObjectiveTo explore the sensitivity and specificity of plasma GAGs for detection of early-stage RCC and prediction of recurrence and death after RCC surgery. Design, setting, and participantsThis was a retrospective case-control study consisting of a consecutive series of 175 RCC patients surgically treated between May 2011 and February 2014 and 19 healthy controls. Outcome measurements and statistical analysisPlasma GAGs in preoperative and postoperative RCC and healthy samples were measured using capillary electrophoresis with laser-induced fluorescence in a single blinded laboratory. A discovery set was first analyzed to update the historical GAG score. The sensitivity of the new GAG score for RCC detection versus healthy subjects was validated using the remaining samples. The correlation of the new GAG score to histopathologic variables, overall survival, and recurrence-free survival was evaluated using nonparametric and log-rank tests and multivariable Cox regression analyses. Results and limitationsThe RCC cohort included 94 stage I, 58 stage II–III, and 22 stage IV cases. In the first discovery set (n=67), the new GAG score distinguished RCC from healthy samples with an area under the receiver operating characteristic curve (AUC) of 0.999. In the validation set (n=108), the GAG score achieved an AUC of 0.991, with 93.5% sensitivity. GAG scores were elevated in RCC compared to healthy samples, irrespective of and uncorrelated to stage, grade, histology, age, or gender. The total chondroitin sulfate concentration was an independent prognostic factor for both overall and recurrence-free survival (hazard ratios 1.51 and 1.25) with high concordance when combined with variables available at pathologic diagnosis (C-index 0.926 and 0.849) or preoperatively (C-index 0.846 and 0.736). Limitations of the study include its retrospective nature and moderate variability in GAG laboratory measurements. ConclusionsPlasma GAGs are highly sensitive diagnostic and prognostic biomarkers in surgically treated RCC independent of stage, grade, or histology. Prospective validation studies on GAG scores for early detection, prediction, and surveillance for RCC recurrence are thus warranted. Patient summaryIn this study, we examined if a new molecular blood test can detect renal cell carcinoma in the early stages and predict if the cancer might relapse after surgery.The trial is registered on ClinicalTrial.gov as NCT03471897.

Society of Abdominal Radiology disease-focused panel on renal cell carcinoma: update on past, current, and future goals.

The disease-focused panel (DFP) program was created by the Society of Abdominal Radiology (SAR) as a mechanism to "improve patient care, education, and research" in a "particular disease or a particular aspect of a disease". The DFP on renal cell carcinoma (RCC) was proposed in 2014 and has been functional for 4years. Although nominally focused on RCC, the scope of the DFP has included indeterminate renal masses because many cannot be assigned a specific diagnosis when detected. Since its founding, the DFP has been active in a variety of clinical, research, and educational projects to optimize the care of patients with known or suspected RCC. The DFP is utilizing multi-institutional and cross-disciplinary collaboration to differentiate benign from malignant disease, optimize the management of early stage RCC, and ultimately to differentiate indolent from aggressive cancers. Several additional projects have worked to develop a quantitative biomarker that predicts metastatic RCC response to anti-angiogenic therapy. While disease focus is the premise by which all DFPs are created, it is likely that in the future the RCC DFP will need to expand or create new panels that will focus on other specific aspects of RCC-a result that the program's founders envisioned. New knowledge creates a need for more focus.

The tumor suppressor role of microRNA-338-3p in renal cell carcinoma.

Human renal cell carcinoma (RCC) is the most common type of kidney malignancy in adults accounting for 2–3% of all adult malignancies. In China, RCC accounts for ~0.5% of all cancer-associated mortalities, ranking 16th among all cancer types. For early-stage RCC, surgery is the recommended treatment. Molecularly targeted therapy is the preferred first-line treatment for clear-cell RCC. However, more potential targets are required. MicroRNA-338-3p (miR-338-3p) functions as a tumor suppressor in various cancers, but has not been studied in RCC. Accordingly, the present study investigated the role of miR-338-3p of RCC. It was demonstrated that miR-338-3p was present at low levels in RCC tissues. Also, overexpression of miR-338-3p inhibited cell proliferation and promoted cell apoptosis, and downregulation of miR-338-3p promoted cell proliferation. The 3′ untranslated region of AKT serine/threonine kinase 3 was targeted by miR-338-3p. In conclusion, the data of the present study revealed the inhibitory function of miR-338-3p in RCC and suggested that miR-338-3p is novel therapeutic target for RCC, but further investigation is needed.

Long noncoding RNA GIHCG is a potential diagnostic and prognostic biomarker and therapeutic target for renal cell carcinoma.

Long noncoding RNA (lncRNA) GIHCG has been reported as an oncogene in hepatocellular carcinoma. However, the expression, roles, and clinical values of GIHCG in renal cell carcinoma (RCC) remain unclear. The aim of this study was to investigate the expression, roles, diagnostic and prognostic values of GIHCG in RCC. The expression of GIHCG in 46 pairs of RCC tissues and adjacent normal renal tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). GIHCG serum level in 46 RCC patients, 46 age- and sex-matched healthy controls, 20 pre- and post-surgery RCC patients was measured by qRT-PCR. The diagnostic values of serum GIHCG were evaluated by receiver operating characteristic (ROC) curves analysis. The effect of GIHCG on RCC cell proliferation was evaluated using Cell Count Kit-8 assay, and the effect of GIHCG on RCC cell migration was evaluated using transwell migration assay. GIHCG is upregulated in RCC tissues compared with adjacent normal renal tissues. Increased expression of GIHCG is positively correlated with advanced TNM stages, Fuhrman grades, and poor prognosis. Serum GIHCG level is also significantly upregulated in RCC patients and correlated with advanced TNM stages. Serum GIHCG could accurately discriminate RCC patients from healthy controls, and also early stage RCC patients from healthy controls. Furthermore, serum GIHCG level is positively correlated with GIHCG expression in RCC tissues. Serum GIHCG level is significantly reduced after radical resection of RCC. Functional assays showed that knockdown of GIHCG significantly represses proliferation and migration of RCC cells. Long noncoding RNA GIHCG would sever as a novel diagnostic and prognostic biomarker and therapeutic target for RCC.

P093 - Plasma glycosaminoglycan scores in early stage renal cell carcinoma

P093 - Plasma glycosaminoglycan scores in early stage renal cell carcinoma

Renal Autotransplantation and Extracorporeal Nephron-Sparing Surgery for De Novo Renal Cell Carcinoma in a Kidney Allograft.

De novo renal cell carcinoma (RCC) rarely occurs in kidney allografts; however, the risk of RCC in these patients is 100-fold that of the general healthy population. Although total nephrectomy has been the standard treatment for kidney allograft RCC, several authors have reported that early-stage RCC in kidney allografts was successfully treated with nephron-sparing surgery. We herein describe a new procedure involving renal autotransplantation and extracorporeal nephron-sparing surgery, which was performed to treat de novo RCC near the hilum of a transplanted kidney. In the 22 months since transplantation, the patient's renal function has been favorable, and no recurrence has been observed. In conclusion, renal autotransplantation is a feasible technique for the treatment of RCC in kidney allografts, especially RCC located near the hilum.

Kidney Cancer Incidence in California: End of the Trend?

Background and Objective: Since the 1990s, multiple studies have reported on an increased incidence of renal cell carcinomas (RCC), which has been considered incidental to the high use of abdominal diagnostic imaging. This population-based study used data from the California Cancer Registry to (i) update trends in RCC incidence and mortality by several tumor and demographic characteristics after reports of decreased use of diagnostic imaging in recent years, and (ii) examine changes in surgical treatment for early-stage RCC.Methods: Records of patients diagnosed with RCC from 1988 through 2013 and mortality data from the same period were examined. Joinpoint regression was used to estimate annual percent changes in age-adjusted RCC incidence and mortality rates, stratified by sex, race/ethnicity, stage at diagnosis, grade, and tumor size. Trends in the proportion of partial or total/radical nephrectomies were evaluated by Cochran-Armitage tests.Results: A total of 77,363 incident cases of RCC and 28,590 deaths were evaluated. While mortality rates significantly decreased, the incidence of small localized RCC increased in virtually all groups examined after the mid-1990s until 2008-2009, when incidence trends stabilized in all groups concomitant with a decrease in imaging. The proportion of partial nephrectomies among patients with small localized tumors increased from 13.8% in 1988 to 74.6% in 2013.Conclusions: Earlier trends in RCC were consistent with the incidental discovery of small tumors. In parallel with the increase in early-stage RCC, the use of partial nephrectomies increased markedly. Following the decreased use of advanced diagnostic imaging, the trend of increasing RCC incidence appears to have ended in California.

USP21 regulates Hippo pathway activity by mediating MARK protein turnover.

The Hippo pathway, which acts to repress the activity of YAP and TAZ trancriptional co-activators, serve as a barrier for oncogenic transformation. Unlike other oncoproteins, YAP and TAZ are rarely activated by mutations or amplified in cancer. However, elevated YAP/TAZ activity is frequently observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components and deubiquitylating enzymes that counteract these ubiquitin ligases have been implicated in human cancer. Here we identify the USP21 deubiquitylating enzyme as a novel regulator of Hippo pathway activity. We provide evidence that USP21 regulates YAP/TAZ activity by controlling the stability of MARK kinases, which promote Hippo signaling. Low expression of USP21 in early stage renal clear cell carcinoma suggests that USP21 may be a useful biomarker.

Mitochondrial DNA copy number variation as a potential predictor of renal cell carcinoma.

Peripheral blood mitochondrial DNA (mtDNA) copy number alteration has been suggested as a risk factor for several types of cancer. The aim of the present study was to assess the role of peripheral blood mtDNA copy number variation as a noninvasive biomarker in the prediction and early detection of renal cell carcinoma (RCC) in a cohort of Egyptian patients. Quantitative real-time polymerase chain reaction (qPCR) was used to measure peripheral blood mtDNA copy numbers in 57 patients with newly diagnosed, early-stage localized RCC and 60 age- and sex-matched healthy individuals as a control group. Median mtDNA copy number was significantly higher in RCC cases than in controls (166 vs. 91, p<0.001). Increased mtDNA copy number was associated with an 18-fold increased risk of RCC (95% confidence interval: 5.065-63.9). On receiver operating characteristic curve analysis, it was found that mtDNA could distinguish between RCC patients and healthy controls, with 86% sensitivity, 80% specificity, 80.3% positive predictive value and 85.7% negative predictive value at a cutoff value of 108.5. Our results showed that increased peripheral blood mtDNA copy number was associated with increased risk of RCC. Therefore, RCC might be considered as part of a range of potential tumors in cases with elevated blood mtDNA copy number.

Microwave ablation of malignant renal tumours: intermediate-term results and usefulness of RENAL and mRENAL scores for predicting outcomes and complications.

The aim of this study was to evaluate intermediate-term results after microwave ablation (MWA) of renal tumours and determine the association of RENAL and modified RENAL (mRENAL) scores with oncological outcomes and complications. In May 2008-September 2014, 58 patients affected by early-stage RCC (renal cell carcinoma; T1a or T1b) were judged unsuitable for surgery and treated with percutaneous MWA. Follow-up was performed with contrast-enhanced computed tomography at 1, 3, 6, 12 and 24months after the procedure. Technical success (TS), primary technical effectiveness (PTE), secondary technical effectiveness (STE), the local tumour progression rate (LTPR), the cancer-specific survival rate (CSSR), disease-free survival (DFS), overall survival (OS) and safety were recorded. All lesions were evaluated using RENAL and mRENAL scores, and complications were assessed with RENAL scores. The TS rate was 100%, PTE was 93%, STE was 100%, LTPR was 15.7% at 1year, CSSR was 96.5%, DFS was 87.9% at 5years, and OS was 80.6%. Mean follow-up was 25.7months (range 3-72). The mean±standard deviation (SD) RENAL and mRENAL scores of all treated tumours were 6.7±2.05 (range 4-11) and 7±2.3 (range 4-12), respectively. Major complications occurred in two (2/58) and minor complications in three patients (3/58). Overall complications correlated significantly with RENAL scores; in particular, E and L represent negative predictors for safety and effectiveness. MWA is a valuable alternative for treating RCCs. The correlation with outcomes and complications of RENAL and mRENAL scores could help to customise MWA indications in RCC patients.

Second Primary Cancer Risk among Kidney Cancer Patients in Korea: A Population-Based Cohort Study.

PurposeSecondary primary cancers (SPCs) commonly arise in patients with renal cell carcinoma (RCC). We designed the present study to estimate the SPC incidence in Korean patients with RCC.Materials and MethodsThe study cohort was population-based and consisted of 40,347 individuals from the Korean Central Cancer Registry who were diagnosed with primary renal cancer between 1993 and 2013. Standardized incidence ratios (SIRs) for SPCs were estimated for different ages at diagnosis, latencies, diagnostic periods, and treatments.ResultsFor patients with primary RCC, the risk of developing a SPC was higher than the risk of developing cancer in the general population (SIR, 1.13; 95% confidence interval, 1.08 to 1.18). Most cancer types showed higher incidences in patients with RCC than in the general population. However, the relative incidence of gastric cancer as an SPC varied by age. Gastric cancer incidence was elevated in young patients (< 30 years) with RCC, but reduced in older (≥ 30) patients with RCC. Patients with advanced RCC died prematurely, regardless of SPC development. In contrast, those with early-stage RCC survived for longer periods, although SPC development affected their post-RCC survival. After SPC development, women had better survival than men.ConclusionIn Korean patients with primary RCC, the incidence of SPC was 13% higher than the incidence of cancer in the general population. These findings may play important roles in the conduct of follow-up evaluations and education for patients with RCC.

Clinical relevance of aortic calcification in urolithiasis patients

BackgroundThe aim of the present study is to investigate the clinical relevance of aortic calcification in urolithiasis patients.MethodsBetween January 2010 and September 2014, 1221 patients with urolithiasis were treated in Oyokyo Kidney Research Institute and Hirosaki University Hospital. Among these, 287 patients (Stone group) on whom adequate data were available were included in this retrospective study. We also selected 148 subjects with early stage (pT1N0M0) renal cell carcinoma from 607 renal cell carcinoma patients who underwent radical nephrectomy at Hirosaki University Hospital (Non-stone group) as control subjects. Validity of the Non-stone group was evaluated by comparison with pair-matched 296 volunteers from 1166 subjects who participated in the Iwaki Health Promotion Project in 2014. Thereafter, age, body mass index, aortic calcification index (ACI), renal function, serum uric acid concentrations, and comorbidities (diabetes, hypertension, or cardiovascular disease) were compared between the Non-stone and Stone groups. Independent factors for higher ACI and impaired renal function were assessed using multivariate logistic regression analysis.ResultsWe confirmed relevance of Non-stone group patients as a control subject by comparing the pair-matched community-dwelling volunteers. Backgrounds of patients between the Non-stone and Stone groups were not significantly different except for the presence of hypertension in the Stone group. ACI was not significantly high in the Stone group compared with the Non-stone group. However, age-adjusted ACI was greater in the Stone group than the Non-stone group. Among urolithiasis patients, ACI was significantly higher in uric acid containing stone patients. The number of patients with stage 3B chronic kidney disease (CKD) was significantly higher in the Stone group than in the Non-stone group (12% vs. 4%, P = 0.008). Multivariate logistic regression analysis showed higher aortic calcification index (>13%), and being a stone former were independent factors for stage 3B CKD at the time of diagnosis.ConclusionAortic calcification and being a stone former had harmful influence on renal function. This study was registered as a clinical trial: UMIN: UMIN000022962.

Safety and effectiveness of percutaneous radiofrequency ablation in early stage renal cell carcinoma.

The purpose of this study was to analyze the safety and effectiveness of percutaneous radiofrequency ablation (RFA) in early stage renal cell carcinoma. A total of 76 patients suffering from early stage renal cell carcinoma were selected and randomly assigned into the observation group (41 cases) or the control group (35 cases). Percutaneous RFA was used in the observation group, while retroperitoneoscopic radical operation of renal cell carcinoma was used in the control group, and the operative effects were compared. In the observation group, operation time, blood loss during operation, length of stay and incidence rate of complications were lower than those in control group (P<0.05). For both groups, serum C-reactive protein, interleukin-6 and T lymphocyte counts at 1, 2 and 3 days after operation were all increased; however, the control group had significantly greater increase for all the time points (P<0.05). For total effective rates, tumour-free survival times and survival rates, there were no statistically significant differences between the two groups (P>0.05). Percutaneous RFA has a reduced size of operation wound and a quick postoperative recovery time in the treatment of early stage renal cell carcinoma. It results in less inflammation and immunity-based injuries in the body and achieves the same clinical outcomes as retroperitoneoscopic radical operation of renal cell carcinoma.

Sorafenib improves the postoperative effect of early stage renal cell carcinoma.

Sorafenib was examined to determine whether it improves postoperative effects during early stage renal cell carcinoma (RCC). A total of 133 patients with early renal clear cell carcinoma (T1-2N0M0) with surgical indications were continuously selected. The patients were divided into 3 groups according to different treatments, including the surgery alone group (40 cases), surgery combined with cytokine group (45 cases) and surgery combined with sorafenib group (48 cases), to make a comparison of their clinical effects. The surgery combined with sorafenib group significantly reduced the recurrence rate and increased the survival rate (P<0.05). Its median survival period was >30 months and the other 2 groups were 27 months (P<0.05). In the subsequent 3 months patients were followed up and it was found that the creatinine levels were significantly elevated and hemoglobin levels were significantly decreased. The sorafenib group had significantly lower creatinine levels and higher hemoglobin levels than the other 2 groups (P<0.05). In the 3-month follow-up, vascular endothelial growth factor (VEGF) levels were significantly reduced and tumor necrosis factor (TNF)-α levels were elevated, although the sorafenib group had significantly decreased VEGF levels and a higher TNF-α level than the other 2 groups (P<0.05). The adverse reaction rate was significantly lower than that of the surgery combined with cytokines group (P<0.05). In conclusion, sorafenib improves the early RCC postoperative survival rate and prolongs the survival time while reducing the recurrence rate. It does not increase adverse reactions, and improves renal function, by decreasing the level of VEGF, and improving the level of TNF-α.

Prediction and diagnosis of renal cell carcinoma using nuclear magnetic resonance-based serum metabolomics and self-organizing maps.

Diagnosis of renal cell carcinoma (RCC) at an early stage is challenging, but it provides the best chance for cure. We aimed to develop a predictive diagnostic method for early-stage RCC based on a biomarker cluster using nuclear magnetic resonance (NMR)-based serum metabolomics and self-organizing maps (SOMs). We trained and validated the SOM model using serum metabolome data from 104 participants, including healthy individuals and early-stage RCC patients. To assess the predictive capability of the model, we analyzed an independent cohort of 22 subjects. We then used our method to evaluate changes in the metabolic patterns of 23 RCC patients before and after nephrectomy. A biomarker cluster of 7 metabolites (alanine, creatine, choline, isoleucine, lactate, leucine, and valine) was identified for the early diagnosis of RCC. The trained SOM model using a biomarker cluster was able to classify 22 test subjects into the appropriate categories. Following nephrectomy, all RCC patients were classified as healthy, which was indicative of metabolic recovery. But using a diagnostic criterion of 0.80, only 3 of the 23 subjects could not be confidently assessed as metabolically recovered after nephrectomy. We successfully followed-up 17 RCC patients for 8 years post-nephrectomy. Eleven of these patients who diagnosed as metabolic recovery remained healthy after 8 years. Our data suggest that a SOM model using a biomarker cluster from serum metabolome can accurately predict early RCC diagnosis and can be used to evaluate postoperative metabolic recovery.

AB148. Urology &amp; reproductive medicine feasibility of dual energy CT unenhanced spectral curve on differential diagnosis between clear cell renal cell carcinoma and renal angiomyolipoma

ObjectiveDue to the lack of typical clinical symptoms and the similarity in radiography of early stage renal cell carcinoma (RCC) and small sized renal angiomyolipoma (RAML), it is usually difficult on the differential diagnosis. In this article, we discovered the feasibility of unenhanced dual energy CT spectral curves in differential diagnosis of RCC and RAML, aiming at providing a new imaging method for the diagnosis and differential diagnosis of RCC and RAML.MethodsSixty-six cases of renal tumor under treatment in our institute were retrospectively studied. All these patients were examined through the dual energy CT. Among those patients, 43 cases were pathologically confirmed as clear cell renal cell carcinoma (CCRCC) and 23 cases were RAML. The regions of interest (ROIs) were set on the cross-sectional image of the tumors. Spectral curves were created based on these ROIs, the average CT values at 40–140 keV and the average slopes of the curves were calculated. According to the slopes, the curves were divided into three types (type I–III). The constituent ratios of each spectral curve types in CCRCC and AML groups were calculated. Statistical approaches were employed to check all the results.Results(I) At 40–140 keV, CT values of CCRCC were higher than RAML, the differences were statistically significant (P=0.00); (II) the difference between the average slope of CCRCC and AML was statistically significant (t=7.31, P=0.00); (III) the constituent ratios of each spectral curve types have shown a statistically significant difference (x2=47.33, P=0.00) between CCRCC and RAML.ConclusionsCCRCC and RAML have significantly different CT values on 40–140 keV and different spectral curve types, unenhanced spectral CT scan provides a new method for diagnosis and differential diagnosis of CCRCC and RAML.