High-grade Renal Cell Carcinoma Research Articles

Invasion and metastasis of renal cell carcinoma

Renal cell carcinoma (RCC) represents over 80% of kidney cancer, and about 30% of the patients with RCC develop metastasis after the surgery. Invasion of basement membrane (BM) and extracellular matrix (ECM) is an essential event in tumor invasion and metastasis. Matrix metalloproteinases (MMPs), which digest the main components of BM and ECM, are expressed in RCC. Heparanase, which degrades heparan sulfate proteoglycans, is predominantly expressed in high-grade RCCs with a positive correlation with pathological tumor stage and poor prognosis. Bone metastasis is common among the patients with RCC, and increased osteoclastic activity was observed at metastatic sites. Receptor activator of nuclear factor κB ligand (RANKL), which plays an important role in osteoclastogenesis, is predominantly expressed in high-grade RCC and its expression level is associated with bone metastasis and prognosis. Epithelial-mesenchymal transition (EMT), a switch of epithelial cells to sarcomatoid phenotype, is considered to be critical step during metastasis, and Snail, a major regulator of EMT, is predominantly expressed in high-grade RCC, and high Snail expression is a worse prognostic factor. Accordingly, heparanase, RANKL and Snail may be targets for the development of anti-tumor therapies for RCCs.

Periampullary and Pancreatic Metastatic Disease of Renal Cell Carcinoma: An Underdiagnosed Disease!

Purpose: The National Cancer Institute reports high incidence of renal cell carcinoma (RCC) in the United States compared to other regions. However, pancreatic and periampullary metastasis are uncommon when only 17% of the RCC cases metastasize overall. We herein present a case series of four patients with periampullary or pancreatic metastatic disease following complete resection of RCC, evaluating their occurrences and outcomes. We reviewed the cases of four male patients retrospectively, mean age 75 years (range 65 to 87 years) who had a previous history of nephrectomy for RCC. They experienced recurrence with periampullary (two patients) or pancreatic (two patients) metastatic disease between 0 to 108 months (mean time 41.5 months) following primary tumor resection. In patients with periampullary metastasis, one had asymptomatic presentation with progressive dilatation of the pancreatic duct noted on surveillance CT scans. The other patient had iron deficiency anemia and melena with EGD findings of large fungating infiltrative ulcerative mass in the area of duodenal papilla (the only patient with metastasis to other sites: lungs and colon). As for those with pancreatic metastasis, one patient presented with hematuria and abdominal pain and was found to have pancreatic metastasis at the time of RCC diagnosis. The other patient was admitted for further workup of a mass in the pancreatic tail upon surveillance. Pathologic findings included high-grade renal cell carcinoma in the metastatic foci. Management of such patients included distal pancreatectomy in two patients without chemoradiation, one is awaiting Whipple procedure and received four cycles of sunitinib, while the last is a poor surgical candidate and received aminocaproic acid. Three patients are still alive to date. Optimal management is challenging given the very high risk of delayed relapse following tumor resection of the localized disease, leaving such cases with a very poor prognosis. Therefore to enhance survival, it is imperative to have careful stage-dependent surveillance in patients who have undergone a prior resection of RCC. We emphasize the importance of raising awareness for this unusual presentation. Disease recurrence as a pancreatic mass or hepatobiliary ductal dilatation might be more frequent than previously reported.

A population-based competing-risks analysis of survival after nephrectomy for renal cell carcinoma

ObjectivesVariability in survival after surgical treatment is observed in patients with renal cell carcinoma (RCC), thereby affirming the heterogeneity of the disease. The aim of our study was to provide a clinically relevant and detailed assessment of survival following surgical excision in patients with RCC of all stages according to age, stage, and grade. Materials and methodsA retrospective population-based analysis of 42,090 patients in the United States who were treated with partial nephrectomy (PN) or radical nephrectomy (RN) for RCC of all stages between the years 1988 and 2008 was performed. Competing-risks Poisson regression analyses focusing on cancer-specific mortality (CSM) or other-cause mortality (OCM) were executed. Stratification was performed according to age groups (≤59, 60–69, 70–79, and ≥80y), the American Joint Committee on Cancer stage (I, II, III, and IV), and the Fuhrman grade (I–II and III–IV). ResultsIncreasing stage was associated with higher CSM rates (from 2%–9% to 54%–79% for stage I and IV), regardless of age. Similarly, high tumor grade was associated with higher CSM rates (from 2%–64% to 6%–79% for low and high grade). However, OCM was nonnegligible amongst persons aged 70 to 79 years (11%–24%) and ≥80 years (17%–44%), regardless of stage and grade. In subanalyses focusing on stage I RCC, CSM (3%–10%) rates were slightly higher for RN-treated patients, regardless of age and grade. However, in individuals aged 70 to 79 years with high-grade RCC, OCM rates were slightly higher for PN relative to RN (25.5% vs. 23.5%). In those aged ≥80 years, OCM rates were higher for PN compared with RN, both for low-grade (39.4% vs. 32.7%) and high-grade disease (52.0% vs. 42.8%). ConclusionsTumor grade and American Joint Committee on Cancer stage represent important prognostic factors for the prediction of CSM, despite adjustment for patient age. However, OCM rates were nonnegligible in elderly individuals (≥70y) with low-grade and stage I to III RCC.

External validation of the RENAL nephrometry score nomogram for predicting high-grade renal cell carcinoma in solid, enhancing, and small renal masses

To confirm predictive accuracies of the RENAL nephrometry score (RNS) nomogram for identifying malignancy and high-grade renal cell carcinoma (RCC) in an external cohort of small renal masses (SRMs). A total of 1,129 patients who underwent extirpative renal surgery for solid and enhancing cT1 renal tumors between 2005 and 2012 at a single institution were included in the validation cohort. A single uro-radiologist utilized computed tomography image reconstruction to classify tumors according to the RNS. The area under the curve (AUC) and calibration plots were used to determine predictive accuracies of malignancy and high-grade models of the RNS nomogram. Malignant and high-grade tumors were identified in 1,012 (89.6%) and 389 (38.4%) patients with cT1 tumors, and in 658 (87.3%) and 215 (32.6%) patients with cT1a tumors, respectively. Predictive performances of the nomogram for malignancy and high-grade models revealed AUCs of 0.722 and 0.574 for cT1 tumors, and 0.727 and 0.495 for cT1a tumors, respectively. The predictive value of the malignancy model was comparable to that of the model-development cohort (AUC = 0.76); however, the predictive value of the high-grade model was inferior to that of the model-development cohort (AUC = 0.73). Unlike previous validation studies, we report inferior predictive performance of the RNS nomogram for discriminating high-grade RCC in solid and enhancing SRMs. This suggests that the RNS nomogram may be unreliable for preoperatively predicting high-grade RCC in SRMs, in which tumor size, the key determinant of high-grade RCC, is a limiting factor.

736 RCC GRADE PREDICTION USING CONTRASTED COMPUTED TOMOGRAPHY

You have accessJournal of UrologyKidney Cancer: Evaluation & Staging (II)1 Apr 2013736 RCC GRADE PREDICTION USING CONTRASTED COMPUTED TOMOGRAPHY Luck Hee Sung, Choong Hee Noh, Jae Yong Chung, and Ji Hyung Yu Luck Hee SungLuck Hee Sung seoul, Korea, Republic of More articles by this author , Choong Hee NohChoong Hee Noh seoul, Korea, Republic of More articles by this author , Jae Yong ChungJae Yong Chung seoul, Korea, Republic of More articles by this author , and Ji Hyung YuJi Hyung Yu seoul, Korea, Republic of More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.299AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nuclear grade (Fuhrman) is an independent prognostic factor in renal cell carcinoma (RCC). Contrasted CT is one of the most important tools in the diagnosis and staging of (RCC). The amount of enhancement on contrasted CT to predict high grade tumours can be useful. Our objective was to identify if tumour enhancement was associated to RCC grade. METHODS Medical charts of all patients with histologic diagnosis of RCC and a preoperative contrasted CT on a patient archive communication system (PACS) were analyzed. All CT were performed on a 64-slice Siemens CT. Variables analyzed during contrast and non-contrast CT were Hounsfield units (HU) of renal parenchyma and tumour. During contrast CT special attention was payed to both the points of highest enhancement and to average enhancement of the whole tumour at the point of greatest necrosis (WTH), if applicable. Pathological variables as well as size and stage were analyzed. Student's T test was used for statistical analysis, using commercially available software. RESULTS 30 patients were included. Average tumour enhancement was 86.67 and 56 HU for low-grade (Fuhrman 1 and 2) and high-grade (Fuhrman 3 and 4) tumours, respectively (p=0.022). When considering the average enhancement WTH, low- and high-grade tumours enhanced 89.2 and 51.3 HU (p=0.002). High-grade tumours were also larger than low-grade tumours (89.2 cm vs. 51.3 cm, p=0.009). CONCLUSIONS High-grade RCC was associated to lower enhancement on contrast CT. Lower average enhancement may correlate to the degree of necrosis and could be a useful tool in prediction of higher nuclear grade and worse prognosis. Larger prospective studies are necessary to confirm this association. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e303 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luck Hee Sung seoul, Korea, Republic of More articles by this author Choong Hee Noh seoul, Korea, Republic of More articles by this author Jae Yong Chung seoul, Korea, Republic of More articles by this author Ji Hyung Yu seoul, Korea, Republic of More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Protein gene product 9.5 is diagnostically helpful in delineating high-grade renal cell cancer involving the renal medullary/sinus region from invasive urothelial cell carcinoma of the renal pelvis

The classification of poorly differentiated carcinomas involving the renal medullary/sinus region might be challenging on conventional histomorphologic grounds alone. However, delineation of high-grade renal cell carcinomas such as collecting duct (Bellini) carcinoma from urothelial cell carcinoma of the renal pelvis is critical, as it conveys important therapeutic implications. We assessed the so far neglected differential diagnostic role of protein gene product 9.5, a neuropeptide involved in intracellular proteolysis, in terms of differentiating invasive urothelial cell carcinomas of the renal pelvis from high-grade renal cell carcinomas infiltrating the renal medullary/sinus region. To this aim, 21 invasive urothelial cell carcinomas of the renal pelvis and 27 high-grade renal cell carcinomas (8 renal cell carcinomas with sarcomatoid dedifferentiation and 5 type 1 and 7 type 2 papillary renal cell carcinomas as well as 7 collecting duct carcinomas) were stained with antibodies directed against protein gene product 9.5, CD10, vimentin, CEA, p63, CK5/6, CK7, CK20, PAX2, PAX8, CD117 (c-Kit), AE1/3, α-methyl CoA racemase, actin, and desmin. Briefly, strong protein gene product 9.5 expression was observed in 6 (86%) of 7 collecting duct carcinomas, 8 (67%) of 12 papillary renal cell carcinomas, and 2 (25%) of 8 renal cell carcinomas with sarcomatoid dedifferentiation. Conversely, none of the 21 urothelial cell carcinomas investigated showed protein gene product 9.5 expression. Our findings suggest that protein gene product 9.5, particularly if used in conjunction with p63 and CK5/6, might be helpful in differentiating high-grade renal cell carcinomas from urothelial cell carcinomas of the renal pelvis, whereas its specificity with respect to the histologic subtyping of renal cell carcinomas seems to be low. However, because of the limited number of study cases enrolled in our investigation, our findings need to be validated in the future.

Tumor Complexity Predicts Malignant Disease for Small Renal Masses

Approximately 20% to 30% of suspicious small renal tumors are benign. A significant proportion of malignant tumors are low grade and potentially indolent. We evaluated whether preoperative patient and tumor characteristics are associated with adverse pathological features. A total of 886 patients underwent robot-assisted partial nephrectomy, as done by 1 of 5 high volume surgeons. Demographic and clinical data were compared between patients with benign/malignant disease, clear cell/nonclear cell renal cell carcinoma and high/low grade tumors. Tumor complexity was quantified by R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, hilar and location relative to polar lines) nephrometry score and described as low--4 to 6, intermediate--7 to 9 or high--10 or greater. Logistic regression analyses were performed to test the association between tumor and patient characteristics, and high grade renal cell carcinoma. Subanalyses were done for patients with renal tumors 4 cm or less. High grade renal cell carcinoma was larger and more likely to develop in men. Patients with malignant tumors and with clear cell histology were more likely to have intermediate or high complexity tumors. Increasing tumor complexity independently predicted malignancy, high grade malignancy and clear cell histology on multivariate regression analysis (each p <0.05). Male gender was independently associated with malignancy and high grade renal cell carcinoma. When considering tumors 4 cm or less, tumor complexity predicted malignancy but not tumor grade. High R.E.N.A.L nephrometry score and male gender are associated with an increased risk of malignancy and high grade malignancy in tumors treated with partial nephrectomy.

CRM1 Blockade by Selective Inhibitors of Nuclear Export Attenuates Kidney Cancer Growth

Renal cell carcinoma often presents asymptomatically and patients are commonly diagnosed at the metastatic stage, when treatment options are limited and survival is poor. Since progression-free survival using current therapy for metastatic renal cell carcinoma is only 1 to 2 years and existing drugs are associated with a high resistance rate, new pharmacological targets are needed. We identified and evaluated the nuclear exporter protein CRM1 as a novel potential therapy for renal cell carcinoma. We tested the efficacy of the CRM1 inhibitors KPT-185 and 251 in several renal cell carcinoma cell lines and in a renal cell carcinoma xenograft model. Apoptosis and cell cycle arrest were quantified and localization of p53 family proteins was assessed using standard techniques. KPT-185 attenuated CRM1 and showed increased cytotoxicity in renal cell carcinoma cells in vitro with evidence of increased apoptosis as well as cell cycle arrest. KPT-185 caused p53 and p21 to remain primarily in the nucleus in all renal cell carcinoma cell lines, suggesting that the mechanism of action of these compounds depends on tumor suppressor protein localization. Furthermore, when administered orally in a high grade renal cell carcinoma xenograft model, the bioavailable CRM1 inhibitor KPT-251 significantly inhibited tumor growth in vivo with the expected on target effects and no obvious toxicity. The CRM1 inhibitor protein family is a novel therapeutic target for renal cell carcinoma that deserves further intensive investigation for this and other urological malignancies.

Diffusion-weighted MRI in renal cell carcinoma: A surrogate marker for predicting nuclear grade and histological subtype

Though previous investigators have attempted to evaluate its utility in characterization of focal renal lesions, diffusion-weighted MR imaging (DW MRI) in renal diseases is still an evolving field and its role in predicting the aggressiveness of renal cell carcinoma (RCC) is yet to be established. To assess whether apparent diffusion coefficient (ADC) values can be used to determine the nuclear grade and histological subtype of RCCs and to identify the tumor attributes contributing to variation in ADC values. The institutional ethics committee waived the requirement of informed consent for this retrospective study. The study cohort consisted of 33 patients who underwent MRI (with diffusion-weighted imaging at b values of 0 and 500 s/mm(2)) and were found to have 36 pathologically-proven RCCs. ADC values were determined for solid portions of RCC, cystic/hemorrhagic areas, and normal renal parenchyma. Histological subtype, nuclear grade, and cell count were determined for each lesion. ADC values were compared between different grades and subtypes and correlation with cell count was investigated. Receiver operating characteristic curves were drawn to establish cut-off ADC values. There were 23 low grade (grades I and II) and 13 high grade tumors (grades III and IV). There were 32 clear-cell and four non-clear-cell RCCs. A decreasing trend of ADC values was seen with increasing grade and mean ADC of high grade RCC was significantly lower than low grade (1.3145 vs 1.6982 × 10(-3) mm(2)/s) (P = 0.005). Mean ADC for clear-cell RCC was significantly higher than non-clear-cell RCC (1.6245 vs. 1.0412 × 10(-3) mm(2)/s) (P = 0.005). ADC values higher than 1.7960 × 10(-3) mm(2)/s were seen only with low grade and values greater than 1.4904 × 10(-3) mm(2)/s were seen only with clear-cell RCC. ADC values provide a non-invasive means to predict the nuclear grade and histological subtype of RCC. Cellularity and morphology are other tumor attributes contributing to the variation in ADC values of RCCs.

External Validation of a Nomogram Using RENAL Nephrometry Score to Predict High Grade Renal Cell Carcinoma

A novel nomogram using the RENAL ([R]adius maximal diameter in cm, [E]xophytic/endophytic properties, [N]earness of the tumor to the collecting system or sinus in mm, [A]nterior/Posterior, [L]ocation relative to the polar lines and [H]ilar) nephrometry score was developed to predict high grade renal cell carcinoma. It showed good performance in internal evaluation. We externally validated the prediction model. We identified a cohort of 391 Chinese patients in whom renal cell carcinoma was surgically resected at our institution from 2008 to 2011. Fuhrman grade was reviewed by an experienced genitourinary pathologist and radiological images were independently assessed by 2 senior urologists. Using a 2-tiered system high grade disease was defined as Fuhrman grade III/IV. The statistical performance of the prediction model was evaluated by discrimination, calibration and clinical usefulness. Of the 391 patients 45.5% were considered to have high grade tumors. External validation of the nomogram revealed an AUC of 0.73. The calibration plot showed that the predicted probability of high grade disease had concordance comparable to the observed frequency. On decision curve analysis the prediction model provided a superior net benefit and reduction at a greater than 20% probability threshold. We confirm the predictive value of the nomogram using the RENAL nephrometry score to identify high grade renal cell carcinoma in an independent cohort. Further research is required to evaluate its performance using a head-to-head comparison with renal biopsy results.

84 A population-based competing-risks analysis of survival after nephrectomy for renal cell carcinoma

Objectives: Variability in survival after surgical treatment is observed in patients with renal cell carcinoma (RCC), thereby affirming the heterogeneity of the disease. The aim of our study was to provide a clinically relevant and detailed assessment of survival following surgical excision in patients with RCC of all stages according to age, stage, and grade. Materials and methods: A retrospective population-based analysis of 42,090 patients in the United States who were treated with partial nephrectomy (PN) or radical nephrectomy (RN) for RCC of all stages between the years 1988 and 2008 was performed. Competing-risks Poisson regression analyses focusing on cancer-specific mortality (CSM) or other-cause mortality (OCM) were executed. Stratification was performed according to age groups (≤59, 60–69, 70–79, and ≥80 y), the American Joint Committee on Cancer stage (I, II, III, and IV), and the Fuhrman grade (I–II and III–IV). Results: Increasing stage was associated with higher CSM rates (from 2%–9% to 54%–79% for stage I and IV), regardless of age. Similarly, high tumor grade was associated with higher CSM rates (from 2%–64% to 6%–79% for low and high grade). However, OCM was nonnegligible amongst persons aged 70 to 79 years (11%–24%) and ≥80 years (17%–44%), regardless of stage and grade. In subanalyses focusing on stage I RCC, CSM (3%–10%) rates were slightly higher for RN-treated patients, regardless of age and grade. However, in individuals aged 70 to 79 years with high-grade RCC, OCM rates were slightly higher for PN relative to RN (25.5% vs. 23.5%). In those aged ≥80 years, OCM rates were higher for PN compared with RN, both for low-grade (39.4% vs. 32.7%) and high-grade disease (52.0% vs. 42.8%). Conclusions: Tumor grade and American Joint Committee on Cancer stage represent important prognostic factors for the prediction of CSM, despite adjustment for patient age. However, OCM rates were nonnegligible in elderly individuals (≥70 y) with low-grade and stage I

A Stage-for-Stage and Grade-for-Grade Analysis of Cancer-Specific Mortality Rates in Renal Cell Carcinoma According to Age: A Competing-Risks Regression Analysis

BackgroundThe association of advanced age and cancer control outcomes shows discordant findings. ObjectiveTo evaluate the effect of age on cancer control outcomes in a large population-based cohort of patients diagnosed with renal cell carcinoma (RCC) of all stages. Design, setting, and participantsUsing the Surveillance Epidemiology and End Results database, 36 333 patients with RCC were identified. The population was stratified according to age:<50, 50–59, 60–69, 70–79, and ≥80 yr. The effect of age on cancer control outcomes was evaluated using competing-risks regression models. Analyses were repeated stage for stage and grade for grade. MeasurementsCancer-specific mortality (CSM) was measured. Results and limitationsAge categories 50–59, 60–69, 70–79, and ≥80 yr respectively portended a 1.4-, 1.5-, 1.6-, and 1.9-fold higher risk of CSM than age category <50 yr (all p < 0.001). The effect of advanced age was particularly detrimental in patients with stage I disease: 1.8-, 2.3-, 3.2-, and 3.8-fold higher CSM risk for the same age groups, respectively (all p<0.001). The effect of age on CSM was at its peak in patients with stage I, low-grade RCC (1.6-, 2.2-, 3.6-, and 4.3-fold, respectively; all p<0.001) and remained elevated in stage I, high-grade RCC (2.2-, 2.6-, 2.4-, and 3.0-fold higher, respectively; all p<0.05). Conversely, its effect was virtually absent in patients with stage II–IV RCC. ConclusionsOur data suggest that stage I RCC may behave in a more aggressive fashion in elderly patients. Further studies are required to confirm the current findings.

Pax-2 antigene expression in kidney tumours

Pax-2 transcriptional factor is expressed during kidney development and could re-express in renal tumors. The aim of this study was to examine Pax-2 expression in different types of renal cell carcinoma (RCC) in order to see whether it is good immunohistochemical marker. We analyzed 48 different renal tumours stained with Pax-2 antibody. Pax-2 positive reaction was noticed in nucleus or cytoplasm. Expression of this antigen in tumours tissue was correlated with tumour stage and nuc-lear grade. Pax-2 expression between different histological RCC types was analyzed by chi2 test and Fishers test for two in-depended samples. Pax-2 is expressed by a high percentage of re-nal tumors regardless of histologic type. Significant diffe-rence of Pax-2 expression between oncocytomas and chromofobe RCC was found. Nuclear expression of Pax-2 is useful diagnostic kidney tumour marker. Pax-2 showed stronger expression in lower malignancy kidney tumours and in oncocytomas, than in high grade RCC like in those with sarcomatoid differentiation

Partial Nephrectomy in a Patient with a Left Ventricular Assist Device

Left ventricular assist device (LVAD) use has increased as a bridge to heart transplant as well as destination therapy in patients with severe heart failure. Presence of LVAD is not a contraindication to noncardiac surgery but does present special challenges to the surgical, anesthesia, and cardiac teams. We present the case of a 40-year-old woman with idiopathic cardiomyopathy necessitating LVAD who underwent left partial nephrectomy for a renal mass. She had undergone three nondiagnostic percutaneous image-guided biopsies. Left partial nephrectomy was performed. Perioperative care was without incident due to careful oversight by a multidisciplinary team. Pathology revealed high-grade clear cell renal cell carcinoma (RCC) with negative margins. Polytetrafluoroethylene (PTFE) bolsters were misidentified six months postoperatively on computed tomography (CT) at an outside institution as a retained laparotomy sponge. This is, to our knowledge, the first report of a partial nephrectomy performed in a patient with LVAD.

Clinico-radio-pathologic features of a solitary solid renal mass at MDCT examination

incidental detection of solid renal masses has been increasing since the multidetector computed tomography (MDCT) scanner was introduced. to evaluate the clinico-radio-pathologic features of a solitary solid renal mass at MDCT examination. a total of 466 non-fatty solid renal masses in 466 patients undergoing nephrectomy were evaluated by MDCT examination. MDCT was performed before and after intravenous injection of contrast material. We obtained the incidences of benign tumors versus malignant tumors, renal cell carcinoma (RCC) versus non-RCC, and asymptomatic RCCs versus symptomatic RCCs. MDCT accuracy for detection of RCC was obtained with a threshold of more than 20 HU tumor attenuation difference between unenhanced and contrast-enhanced CT images. Nuclear grade was also compared between small RCCs (≤4 cm) and large RCCs (>4 cm). of 466 tumors, 443 (95%) were malignant and 23 (5%) were benign. Of 443 malignant tumors, 437 (99%) were RCC and 6 (1%) were non-RCC. Of 437 RCCs, 324 (74%) were asymptomatic and 113 (26%) were symptomatic. Asymptomatic RCCs (n=183, 56%) were more frequently pT1a than symptomatic RCCs (n=28, 25%) (P<0.05). MDCT accuracy for detection of RCC was 94% (437/466). Of 220 RCCs ≤4 cm, low grade RCC (53%) was more common than high grade RCC (47%). most solitary solid renal masses are early stage RCCs and can be diagnosed preoperatively at MDCT examination.

Sex, Age, and Surgeon Decision on Nephron-sparing Surgery Are Independent Predictors of Renal Masses With Benign Histologic Findings—A Multicenter Survey

To define the preoperative independent predictors indicating that renal mass has benign histologic features. A total of 1664 patients with Stage T1-T2N0M0 with a unilateral renal mass underwent nephrectomy. The endpoint at multivariate analysis was benign versus malignant histologic features. The surgical approach (odds ratio [OR] 2.9, P = .0001), sex (OR 1.97, P = .0001), and age (OR 1.01, P = .007) were independent predictors for the malignant-benign distinction. Malignant tumors were more likely to occur in men (878 of 1009, 87%) versus women (515 of 651, 79%; P <.001). A weak relationship was found between an increasing tumor size and malignancy risk in men only. High-grade renal cell carcinoma was more prevalent in men (31% versus 21%, P = .001). The histologic tumor types were distributed differently between the 2 sexes: 8% papillary renal cell carcinoma in women versus 16% in men, 86% and 78% clear cell renal cell carcinoma, 33% and 57% oncocytoma, and 40% versus 12% angiomyolipoma, respectively. The physician's preoperative judgment regarding tumor amenability for nephron-sparing surgery resulted in patient selection: 10% benign tumors for radical nephrectomy versus 25% for partial nephrectomy (P = .001) and 31% versus 20% high-grade tumors, respectively (P = .0001). Renal tumors were consistently benign in 20% of women, regardless of size. In contrast, in men, the malignancy risk increased slightly with tumor size. The surgeons' preoperative decision regarding nephron-sparing surgery caused a selection bias in favor of benign lesions, regardless of sex. Our findings support the possibility of basing treatment decisions on the preoperative biopsy findings. Such changes could alter current practice and limit treatment of histologically proven benign lesions to surveillance or ablation only.

Liver resection for metastatic disease prolongs survival in renal cell carcinoma: 12-year results from a retrospective comparative analysis

The value of surgical resection of renal cell carcinoma (RCC) liver metastases still remains unclear. Of our study was to evaluate the efficacy of liver resection by comparing patients who could have undergone metastasectomy due to limited disease, but refused surgery. Eighty-eight patients were identified with liver metastases and indication of surgery between 1995 and 2006. In 68 patients, liver resection was performed, 20 patients denied surgery and served as comparison group. Patients were followed for survival. Median age was 58. Median amount of liver metastases was 2 (range 1-30). Median follow-up was 26 months (range 1-187). In both groups, 79% received systemic therapy. The 5-year overall survival rate (OSR-5) after metastasectomy was 62.2% +/- 11.4% (SEM) with a median survival (MS) of 142 (95% confidence interval (CI) 115-169) months. OSR-5 in the control group was 29.3% +/- 22.0% (SEM) with a MS of 27 (95% CI 16-38) months (P = 0.003). MS was 155 (95% CI 133-175) months with metachronous metastases compared to 29 (95% CI 25-33) months in the comparison group (P = 0.001). Low-grade primary RCC had a MS of 155 (95% CI 123-187) months compared to 29 (95% CI 8-50) months without resection (P = 0.0036). High-grade RCC as well as patients with synchronous metastases did not benefit from surgery. Liver metastasectomy is an independent valuable tool in the treatment of metastatic RCC and significantly prolongs patient's survival, even if further systemic treatment is necessary. With the evidence given, patients may benefit from liver metastasis resection if technically feasible.

Angiogenesis in renal cell carcinoma: The role of tumor‐associated macrophages

To explore vascularity and associated molecules in renal cell carcinoma (RCC) and to study their correlations to disease outcome. Tissue samples from 51 Japanese patients with renal cell carcinoma (RCC) were obtained between November 1997 and August 2000. Pyrimidine nucleoside phosphorylase and vascular endothelial growth factor (VEGF) levels of RCC and normal kidney tissue were determined by enzyme-linked immunosorbent assay. Microvessel density (MVD) was measured by immunohistochemistry using anti-factor-VIII-related antigen and CD34. The number of infiltrating tumor-associated macrophages (TAM) was measured by immunohistochemistry using anti-CD68 antibody. Pyrimidine nucleoside phosphorylase and VEGF levels were significantly higher in RCC than in normal kidney tissue. The VEGF level was higher in more progressive (high grade, larger or symptomatic) RCC. Although MVD as determined by the factor VIII level was higher in larger tumors, MVD determined by CD34 was higher in low-grade and low-stage tumors. Patients with symptoms, large tumor or high stage showed higher numbers of TAM. VEGF level and TAM were significantly higher in patients with recurrence than in those without recurrence. In univariate analysis, VEGF, TAM and CD34 tumor grade and stage were identified as prognostic factors. Moreover, TAM was the only independent prognostic factor by multivariate analysis. Among these parameters, only TAM and MVD as determined by factor VIII showed significant correlations. TAM and VEGF are substantially involved in tumor progression of RCC. As the TAM count is well correlated to the MVD, the main mechanism of tumor progression by TAM might be angiogenesis.

Capsular involvement in patients undergoing partial nephrectomy for localized renal cell carcinoma: an adverse pathological finding?

To evaluate the prognostic impact of capsular involvement (CaI) in patients treated exclusively with partial nephrectomy (PN) for localized renal cell carcinoma (RCC), as in these patients CaI was recently reported as an adverse prognostic factor. We retrospectively reviewed the medical records of patients treated with PN for a sporadic and localized RCC (pT1-pT2N0M0) in our institution between 1985 and 2005. Univariate and multivariate analysis using a Cox proportional-hazards regression analysis were conducted to identify significant predictors of oncological outcome for several clinical and pathological factors, i.e. imperative indication, histological type, Fuhrman grade, tumour size, T stage, CaI, and surgical margins. Disease-free and -specific survival rates of patients with CaI and no evidence of CaI were compared using the log-rank test. In all, 305 patients had a PN for localized RCC, of whom 22 (7.2%) had CaI in the PN specimen. The median (range) follow-up was 6 (1.5-23) years. Multivariate statistical analysis showed that imperative indication for PN and high-grade RCC were independently associated with worse disease-free and -specific survival, whereas CaI had no prognostic value. Disease-free and -specific survival in patients with and without CaI were not significantly different at 5 and 10 years. In a contemporary series of patients exclusively treated with PN for localized RCC, CaI was not predictive of disease recurrence and disease-specific mortality. These results do not support the use of any change in postoperative management in patients with CaI after PN.

Epithelioid Angiomyolipoma of the Kidney Mimicking Renal Cell Carcinoma: A Clinicopathologic Analysis of Cases and Literature Review

Classical renal angiomyolipoma (AML) is a common tumor that, in most cases, follows a benign course and has clearly defined radiologic and histological characteristics. However, rare cases of clinically aggressive or malignant AML, the epithelioid variant of AML (EAML), have been reported. Here, we review the five cases of EAML diagnosed since 2000 at our institution to highlight the spectrum of clinical, radiological and histological characteristics. In all cases, renal lesions seen on computed tomography (CT) were considered as suspicious for renal cell carcinoma (RCC) without tumor extension or metastasis. One of the two patients with definitive tuberous sclerosis complex had a small conventional AML with fat content in the other kidney. Histologically, these tumors can resemble sarcomatoid RCC or high grade RCC. The final diagnosis is established by the presence of perivascular epithelioid cells and immunohistochemistry markers. There was no evidence of local recurrence or metastatic disease found by sonography, CT and magnetic resonance imaging during the follow-up period. EAMLs are capable of aggressive or malignant clinical behavior. Approximately one third of the reported EAMLs show advanced disease; therefore, we recommend that it is important to treat and closely follow-up such cases, similar to that for RCC, because of its malignant potential.