Perirenal Fat Invasion Research Articles

The role of preoperative immune cell metrics in renal cell carcinoma with a tumor thrombus.

The objective of this study was to stratify preoperative immune cell counts by cancer specific outcomes in patients with renal cell carcinoma (RCC) and a tumor thrombus after radical nephrectomy with tumor thrombectomy. Patients with a diagnosis of RCC with tumor thrombus that underwent radical nephrectomy with thrombectomy across an international consortium of seven institutions were included. Patients who were metastatic at diagnosis and those who received preoperative medical treatment were also included. Retrospective chart review was performed to collect demographic information, past medical history, preoperative lab work, surgical pathology, and follow up data. Neutrophil counts, lymphocyte counts, monocyte counts, neutrophil to lymphocyte ratios (NLR), lymphocyte to monocyte ratios (LMR), and neutrophil to monocyte ratios (NMR) were compared against cancer-specific outcomes using independent samples t-test, Pearson's bivariate correlation, and analysis of variance. One hundred forty-four patients were included in the study, including nine patients who were metastatic at the time of surgery. Absolute lymphocyte count preoperatively was greater in patients who died from RCC compared to those who did not (2 vs 1.4; p < 0.001). Patients with tumor pathology showing perirenal fat invasion had a greater neutrophil count compared to those who did not (7.5 vs 5.5; p = 0.010). Patients with metastatic RCC had a lower LMR compared to those without metastases after surgery (2.5 vs 3.2; p = 0.041). Tumor size, both preoperatively and on gross specimen, had an interaction with multiple immune cell metrics (p < 0.05). Preoperative immune metrics have clinical utility in predicting cancer-specific outcomes for patients with RCC and a tumor thrombus. Additional study is needed to determine the added value of preoperative serum immune cell data to established prognostic risk calculators for this patient population.

Sirtuin 1, as a potential prognosis marker in clear cell renal cell carcinoma, regulates lipid metabolism and immune infiltration.

Clear cell renal cell carcinoma (ccRCC) is a malignancy with a dismal prognosis, caused by the buildup of fat and glycogen. Sirtuin 1 (Sirt1) is a deacetylase that regulates lipid metabolism. In this study, we collected tumor and paracancer tissues from 386 ccRCC patients and followed their prognosis over an extended time period. The expression of Sirt1 in these tissues was assessed using immunohistochemistry, and LinkedOmics database analysis identified differentially expressed genes associated with Sirt1. The survival curve was generated using the Kaplan-Meier method, and immune infiltration was analyzed using the Tumor Immune Estimation Resource (TIMER) web tool. Our findings revealed that Sirt1 was expressed in tumor tissues, but not in normal tissues, and its high expression was associated with a worse prognosis. Furthermore, we observed a positive correlation between high Sirt1 expression and perirenal fat invasion and necrosis, leading to poorer survival outcomes. We established a nomogram to predict prognosis, and a correlation was observed with immune infiltration. In conclusion, our results suggest that high Sirt1 expression is associated with lipid metabolism disorder and immune infiltration, ultimately contributing to a dismal prognosis in ccRCC.

Assessment of Ki-67 proliferation index in prognosis prediction in patients with nonmetastatic clear cell renal cell carcinoma and tumor thrombus

PurposeTo determine the optimal cut-off value of Ki-67 for predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) and tumor thrombus and to explore the correlation between Ki-67 expression and pathological features. Patients and MethodsWe retrospectively analyzed Ki-67 immunohistochemical staining of ccRCC and tumor thrombus resected from February 2006 to February 2022. The survival rate was evaluated using the Kaplan-Meier method. The optimal cut-off value of the Ki-67 expression for predicting survival was determined by the minimum P-value method. Clinicopathological data were compared based on Ki-67 status (low versus high expression). Univariate and multivariate Cox regression analysis was used to explore independent predictors. ResultsA total of 202 patients (median age, 58 years [IQR, 52–65 years], 147 men) with ccRCC and tumor thrombus were included in the study. The optimal cut-off value of Ki-67 for predicting survival was 30%. 159 (78.7%) and 43 (21.3%) patients were included in the low-expression and high-expression groups. Patients with Ki-67 high expression had significantly worse recurrence-free survival (P < 0.001) and cancer-specific survival (P < 0.001). Ki-67 high expression was associated with adverse pathological features, including tumor necrosis, ISUP nuclear grade, sarcomatoid differentiation, perirenal fat invasion, renal pelvis invasion, and inferior vena cava wall invasion (all P < 0.050). Ki-67 expression ≥ 30% (P = 0.016), tumor side (P = 0.003), diabetes (P = 0.040), blood loss (P = 0.016), inferior vena cava wall invasion (P = 0.016), and sarcomatoid differentiation (P = 0.014) were independent predictors of cancer-specific survival. ConclusionThe optimal cut-off level of Ki-67 in predicting the prognosis of ccRCC and tumor thrombus was 30%. The high expression of Ki-67 was associated with the aggressive pathological phenotype and poor prognosis.

Differential Prognostic Value of Extrarenal Involvement in Patients With Non-Metastatic Renal Cell Cancer.

A better definition of the prognostic significance of non-metastatic pT3a stage RCC subcategories is crucial to select the best candidate for adjuvant treatment. The aim of the study is to investigate the differential prognosis of extrarenal involvement in patients with non-metastatic pT3a RCC. From a single institutional prospective database, 451 consecutive patients treated for pT3aN0/NxM0 RCC were selected and stratified according to pT3a subtypes (perirenal fat invasion, sinus fat invasion, segmental/renal vein thrombus, ≥ 2 features). Cancer specific survival (CSS), metastasis free survival (MFS) and relapse free survival (RFS) were primary endpoints of multivariable Cox regression models. Overall, 67 (15%) patients presented with renal/segmental vein thrombus only, 185 (41%) with perirenal fat invasion, 101 (22%) with sinus fat invasion and 98 (22%) with ≥ 2 features. The presence of ≥ 2 pT3a features was associated with a higher risk of metastasis (HR=2.36; 95%CI 1.30-4.27; P value=.005), recurrence (HR=2.41; 95%CI 1.36-4.28; P value=.003) and cancer specific mortality (HR=3.54; 95%CI 1.45-8.63; P value=.005) compared to only 1 pT3a feature. Moreover, the presence of perirenal fat invasion was associated with lower CSS (HR=2.82; 95% CI 1.19-6.69; P value=.02) compared to sinus fat invasion or tumoral thrombus only. The concurrent presence of ≥ 2 pT3a features is associated to a higher risk of distant progression, relapse and cancer specific mortality, implying potential role for adjuvant therapy or a more stringent follow-up. Moreover, perirenal fat invasion is associated with worse CSS compared to other pT3a patterns taken alone.

MP47-17 SINGLE CENTER COMPARISON OF RADIOGRAPHIC AND MORPHOMETRIC CHARACTERISTICS AND OUTCOMES IN T3A PATHOLOGICALLY UPSTAGED AND NON-UPSTAGED RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023MP47-17 SINGLE CENTER COMPARISON OF RADIOGRAPHIC AND MORPHOMETRIC CHARACTERISTICS AND OUTCOMES IN T3A PATHOLOGICALLY UPSTAGED AND NON-UPSTAGED RENAL CELL CARCINOMA Saeed Ghassemzadeh, Aastha Shah, Dhruv Puri, Luke Wang, Franklin Liu, Sohail Dhanji, Kevin Hakimi, Mimi Nguyen, Ryan Nasseri, Margaret Meagher, Clara Cerrato, Juan Javier-Desloges, and Ithaar Derweesh Saeed GhassemzadehSaeed Ghassemzadeh More articles by this author , Aastha ShahAastha Shah More articles by this author , Dhruv PuriDhruv Puri More articles by this author , Luke WangLuke Wang More articles by this author , Franklin LiuFranklin Liu More articles by this author , Sohail DhanjiSohail Dhanji More articles by this author , Kevin HakimiKevin Hakimi More articles by this author , Mimi NguyenMimi Nguyen More articles by this author , Ryan NasseriRyan Nasseri More articles by this author , Margaret MeagherMargaret Meagher More articles by this author , Clara CerratoClara Cerrato More articles by this author , Juan Javier-DeslogesJuan Javier-Desloges More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003293.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A significant portion of patients presenting with Stage 1-2 Renal Cell Carcinoma (RCC) are pathologically upstaged to Stage 3 following surgery. This is due to previously undetected extension into the renal venous system, perirenal or renal sinus fat, or collecting system. Improved detection of potential T3 upstaging may prompt changes in disease management and may impact patient survival. We sought to compare pathologically upstaged and non-upstaged T3a RCC cases to identify characteristics of upstaged masses, predictors of T3a disease, and impact on oncological outcomes. METHODS: We conducted a single center retrospective analysis of patients with pathologic T3a RCC who underwent surgical intervention. The cohort was divided into a group of patients with masses which were upstaged, (cT1-cT2/pT3a) and a group with masses preoperatively identified as cT3a (non-upstaged, cT3a/pT3a) for descriptive and outcomes analyses. We sought to delineate proportion of underdiagnosed pT3a RCC, location of upstaged disease, and predictors of upstaging. Outcomes were overall survival (OS) and recurrence-free survival (RFS). Multivariate analyses (MVA) were performed to identify predictors of T3a invasion site and outcomes. Kaplan Meier survival analyses (KMA) were performed to compare survival outcomes. RESULTS: We analyzed 185 patients, of which 120 (64.9%) were upstaged and 65 (35.1%) were non-upstaged. When compared to non-upstaged masses, upstaged masses were significant for smaller size (6.8 cm vs 8.2 cm, p=0.008), lower RENAL score (8.7 vs 9.9, p<0.001), less hilar involvement (29.2% vs 86.2%, p<0.001), and increased exophyticity (41.7% vs 23.1%, p=0.011). On pathology, upstaged masses had greater proportions of perirenal fat invasion (53.3% vs 33.8%, p=0.011), but less venous system (44.2% vs 78.5%, p<0.001) and sinus fat invasion (35.8% vs 63.1%, p<0.001) compared to non-upstaged masses. RENAL domains R, E, and L were independent predictors for T3a disease foci (OR=0.053-7.70, p=0.001-0.042). MVA demonstrated that non upstaged cT3a RCC had a higher risk of recurrence (HR=2.01, p=0.043). KMA noted better RFS in upstaged patients compared to non-upstaged patients (80.8% vs 75.4%, p=0.002). CONCLUSIONS: Pathologically upstaged T3a RCC is associated with distinct morphology and invasion patterns, and improved recurrence free survival when compared to non-upstaged T3a RCC. RENAL domains can aid in identifying masses with upstaging potential. Source of Funding: UC San Diego Summer Research Fellowship © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e651 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Saeed Ghassemzadeh More articles by this author Aastha Shah More articles by this author Dhruv Puri More articles by this author Luke Wang More articles by this author Franklin Liu More articles by this author Sohail Dhanji More articles by this author Kevin Hakimi More articles by this author Mimi Nguyen More articles by this author Ryan Nasseri More articles by this author Margaret Meagher More articles by this author Clara Cerrato More articles by this author Juan Javier-Desloges More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF downloadLoading ...

A comparison of radiographic and morphometric characteristics and outcomes in T3a pathologically upstaged and non-upstaged renal cell carcinoma.

615 Background: A significant portion of patients presenting with clinically localized stage 1-2 renal cell carcinoma are pathologically upstaged to Stage 3 following surgical intervention. This is due to previously undetected extension into the renal venous system, perirenal or renal sinus fat, or collecting system. Improved detection of potential T3 upstaging may prompt changes in disease management, which may impact patient survival. We sought to compare pathologically upstaged and non-upstaged T3a RCC cases to identify characteristics of upstaged masses, predictors of T3a disease, and impact on oncological outcomes. Methods: We conducted a single center retrospective analysis of patients with pathologic T3a RCC who underwent surgical intervention. The cohort was divided into a group of patients with masses not preoperatively identified as cT3a (upstaged, cT1-cT2/pT3a) and a group of patients with masses preoperatively identified as cT3a (non-upstaged, cT3a/pT3a) for descriptive and outcomes analyses. We sought to delineate proportion of under-diagnosed pT3a RCC, location of upstaged disease, and predictors of upstaging. Primary outcome was overall survival (OS) and secondary outcome was recurrence-free survival (RFS). Multivariate analyses (MVA) were performed to identify predictors of T3a invasion site and outcomes. Kaplan Meier survival analyses (KMA) were performed to compare survival outcomes. Results: We analyzed 185 patients, of which 120 (64.9%) were upstaged and 65 (35.1%) were non-upstaged. When compared to non-upstaged masses, upstaged masses were significant for smaller size (6.8 vs 8.2 cm, p=0.008), lower RENAL score (8.7 vs 9.9, p&lt;0.001), less hilar involvement (29.2% vs 86.2%, p&lt;0.001), and increased exophyticity (41.7% vs 23.1%, p=0.011). On pathology, upstaged masses had greater proportions of perirenal fat invasion (53.3% vs 33.8%, p=0.011), but less venous system (44.2% vs 78.5%, p&lt;0.001) and sinus fat invasion (35.8% vs 63.1%, p&lt;0.001) compared to non-upstaged masses. RENAL domains R (OR=2.30-2.49, p=0.037-0.042), E (OR=0.39-2.32, p=0.003-0.009), and L (OR=0.53-7.70, p=0.001-0.031) were independent predictors for T3a disease foci. MVA demonstrated an association between non-upstaged status and recurrence (HR=2.01, p=0.043) but not overall mortality (HR=1.27, p=0.581). KMA noted better RFS in upstaged patients compared to non-upstaged patients (80.8% vs 75.4%, p=0.002), but no OS differences between upstaged and non-upstaged patients (74.2% vs 83.1%, p=0.209). Conclusions: Pathologically upstaged T3a RCC is associated with distinct morphology and invasion patterns and higher recurrence-free survival outcomes compared to non-upstaged T3a RCC. RENAL domains can assist in identifying masses with upstaging potential, predicting their invasion site, and performing preoperative risk stratification.

A preliminary radiomics model for predicting perirenal fat invasion on renal cell carcinoma with contrast-enhanced CT images.

The aim is to develop a radiomics model based on contrast-enhanced CT scans for preoperative prediction of perirenal fat invasion (PFI) in patients with renal cell carcinoma (RCC). The CT data of 131 patients with pathology-confirmed PFI status (64 positives) were retrospectively collected and randomly assigned to the training and test datasets. The kidneys and the masses were annotated by semi-automatic segmentation. Eight types of regions of interest (ROI) were chosen for the training of the radiomics models. The areas under the curves (AUCs) from the receiver operating characteristic (ROC) curve analysis were used to analyze the diagnostic performance. Eight types of models with different ROIs have been developed. The models with the highest AUC in the test dataset were used for construction of the corresponding final model, and comparison with radiologists' diagnosis. The AUCs of the models for each ROI was 0.783-0.926, and there was no statistically significant difference between them (P > 0.05). Model 4 was using the ROI of the outer half-ring which extended along the edge of the mass at the outer edge of the kidney into the perirenal fat space with a thickness of 3mm. It yielded the highest AUC (0.926) and its diagnostic accuracy washigher than the radiologists' diagnosis. We have developed and validated a radiomics model for prediction of PFI on RCC with contrast-enhanced CT scans. The model proved to bemore accurate than the radiologists' diagnosis.

MP12-06 ONCOLOGIC OUTCOMES IN PATIENTS DIAGNOSED WITH pT3aN0M0 RENAL CELL CANCER ACCORDING TO RENAL VEIN THROMBUS OR FAT INVASION

MP12-06 ONCOLOGIC OUTCOMES IN PATIENTS DIAGNOSED WITH pT3aN0M0 RENAL CELL CANCER ACCORDING TO RENAL VEIN THROMBUS OR FAT INVASION

Nomogram for predicting survival of renal cell carcinoma with tumor thrombus based on perioperative clinicopathological factors from a Chinese high-volume center.

To investigate perioperative clinicopathological predictors and establish a predictive nomogram for survival in patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy. Patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy were included in the study between January 2014 and June 2020. Cox regression analysis was used for univariate and multivariate survival analyses. A predictive nomogram for survival was established and internally validated using bootstrap resampling method. A total of 228 patients were enrolled in this study. The median age was 60 years (interquartile range 53-66 years), consisting of 174 (76.3%) males and 54 (23.7%) females. The median follow-up time was 17.5 months (range 1-74 months), 26.8% (61 of 228) patients died of all causes. In multivariable analysis, hemoglobin less than the lower limit of normal (hazard ratio 1.73; 95% confidence interval 1.01-2.96; P = 0.045), sarcomatoid feature (hazard ratio 3.67; 95% confidence interval 1.97-6.82; P < 0.001), perirenal fat invasion (hazard ratio 1.80; 95% confidence interval 1.05-3.09; P = 0.033), histological subtype (hazard ratio 2.74; 95% confidence interval 1.39-5.41; P = 0.004), and metastasis at surgery (hazard ratio 1.71; 95% confidence interval 1.01-2.90; P = 0.047) were independently associated with overall survival. The result of internal validation presented that the predictive performance of the nomogram for survival measured by C-index was 0.77. We developed a predictive nomogram with well-internal validation for survival in patients with renal cell carcinoma and venous tumor thrombus, which can greatly promote risk stratification and treatment planning.

Predictive features of pre-operative computed tomography and magnetic resonance imaging for advanced disease in renal cell carcinoma.

We evaluated predictive features of pre-operative computed tomography and magnetic resonance imaging for advanced disease in renal cell carcinoma. 92 patients with pathologically confirmed diagnosis of renal cell carcinoma were included in our study. Patients were divided into two groups according to preoperative imaging as computed tomography (CT) (55 patients) and magnetic resonance imaging (MRI) (37 patients). Within the imaging groups, the patients were divided into two groups according to pathological tumor stage: 1-2 (pT1-2) versus ≥ pT3a. It was evaluated whether there was a difference between the two groups in terms of the presence of pre-operative imaging (CT and MRI) features. Predictive value of these features for ≥ pT3a disease was evaluated both for CT and MRI. The cut-off value for the Gerota's fascia thickness in predicting ≥ pT3a disease was calculated as 0.205 cm. Positive predictive value (PPV) for Gerota's fascia thickness was 52.4% (31.0-73.7) and 66.7% (40.0-93.3) for CT and MRI respectively. The PPV value for renal capsule invasion was 75.0% (53.8-96.2) and 90.0% (71.4-108.6) for CT and MRI respectively. PPV of perirenal fat invasion for CT and MRI was 69.2% (44.1-94.3) and 81.8% (59.0-104.6) respectively. Renal capsular invasion and perirenal fat invasion are reliable signs for locally advanced (≥ pT3a) renal cell carcinoma both in CT and MRI. Gerota's fascia thickness has relatively low PPV value for prediction of locally advanced disease. Presence of enlarged collateral vessels, tumor necrosis, perinephric stranding are not reliable signs. For all predictors MRI seems more reliable than CT.

How accurate is radiological imaging for perirenal fat and renal vein invasion in renal cell carcinoma?

To evaluate the accuracy of radiological staging, especially renal venous and perirenal fat invasion, in renal cell carcinoma (RCC). Data of 4823 renal tumour patients from Renal Tumor Database of Association of Uro-oncology in Turkey were evaluated. Of 4823 patients, 3309 RCC patients had complete radiological, and histopathological data were included to this study. The Pearson chi-squared test (χ2 ) was used to compare radiological and histopathological stages. The mean (SD) age of 3309 patients was 58 (12.3). Preoperative radiological imaging was performed using computed tomography (CT) (n=2510, 75.8%) or magnetic resonance imaging (MRI) (n=799, 24.2%). There was a substantial concordance between radiological and pathological staging (к=0.52, P<.001). Sensitivities of radiological staging in stages I, II, III and IV were 90.7%, 67.3%, 27.7% and 64.2%, respectively. The sensitivity in stage III was lower than the other stages. Subanalysis of stage IIIa cases revealed that, for perirenal fat invasion and renal vein invasion, sensitivity values were 15.4% and 11.3%, respectively. There was a substantial concordance between radiological (CT and/or MRI) and pathological T staging in RCC. However, this is not true for T3 cases. Sensitivity of preoperative radiological imaging in patients with pT3a tumours is insufficient and lower than the other stages. Consequently, preoperative imaging in patients with T3 RCC has to be improved, in order to better inform the patients regarding prognosis of their disease.

Prognostic Factors in De Novo Metastatic Renal Cell Carcinoma: A Report From the Latin American Renal Cancer Group.

PURPOSETo assess the effect of clinical and pathological variables on cancer-specific and overall survival (OS) in de novo metastatic patients from a collaborative of primarily Latin American countries.PATIENTS AND METHODSOf 4,060 patients with renal cell carcinoma diagnosed between 1990 and 2015, a total of 530 (14.5%) had metastasis at clinical presentation. Relationships between clinical and pathological parameters and treatment-related outcomes were analyzed by Cox regression and the log-rank method.RESULTSOf 530 patients, 184 (90.6%) had died of renal cell carcinoma. The median OS of the entire cohort was 24 months. American Society of Anesthesiology classification 3-4 (hazard ratio [HR]: 1.64), perirenal fat invasion (HR: 2.02), and ≥ 2 metastatic organ sites (HR: 2.19) were independent prognostic factors for 5-year OS in multivariable analyses. We created a risk group stratification with these variables: no adverse risk factors (favorable group), median OS not reached; one adverse factor (intermediate group), median OS 33 months (HR: 2.04); and two or three adverse factors (poor risk group), median OS 14 months (HR: 3.58).CONCLUSIONOur study defines novel prognostic factors that are relevant to a Latin American cohort. With external validation, these easily discerned clinical variables can be used to offer prognostic information across low- and middle-income countries.

Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma.

PurposeAdvanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism–related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism–related proteins on patient prognoses in advanced stage ccRCCs.Materials and MethodsAll of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation.ResultsFPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival.ConclusionFPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.

The prognostic value of fat invasion and tumor expansion in the hilar veins in pT3a renal cell carcinoma

PurposeThe 7th TNM classification summarizes renal cell carcinoma (RCC) with perirenal (PFI) and/or sinus fat invasion (SFI) as well as hilar vein involvement (RVI) as pT3a tumors. In this study, we aimed to determine the prognostic value of fat invasion (FI) in the different compartments and RVI for medium-term cancer-specific-survival (CSS) in pT3a RCC.Materials and methodsPatients with pT3a RCC were identified using an institutional database. All original pathological reports were reclassified according to the 7th TNM edition. The prognostic value of FI as well as divided into PFI, SFI, combined PFI + SFI, and RVI for CSS was assessed using univariate and multivariate Cox-regression analysis. Survival was estimated using the Kaplan–Meier method.ResultsMedian follow-up in 184 pT3a tumors was 38 months. FI was detectable in 153 patients (32.7% PFI, 45.1% SFI, 22.2% PFI + SFI), 31 patients showed RVI alone. Combined PFI + SFI increased the risk of cancer-related death compared to PFI (HR 3.11, p < 0.01), SFI (HR 1.84, p = 0.023) or sole RVI (HR 2.12, p = 0.025). In multivariate analysis, a combined PFI + SFI vs. PFI or SFI as the only compartment involved was confirmed as independent prognostic factor (HR 1.83, p = 0.029). Patients with FI and simultaneous RVI had significantly shorter CSS (HR 2.63, p < 0.01). In an unweighted model, the difference between patients with combined PFI + SFI and RVI and those with PFI alone was highest (HR 4.01, p = 0.029).ConclusionsThese results underline the subdivision of pT3a RCC depending on the location of FI and RVI for patient stratification.

The Role of EMMPRIN in Perirenal Fat Invasion Clear Cell Renal Cell Carcinoma

Renal Cell Carcinoma (RCC) is a common malignancy of the kidney, and Clear Cell Renal Cell Carcinoma(CCRCC) is the most common type. Accurate prediction of prognosis is valuable for therapy and followup. EMMPRIN is a transmembrane protein of the immunoglobulin family and is associated with tumourproliferation, invasion and metastasis. This study aims to prove the role of EMMPRIN in perirenal fatinvasion CCRCC. This analytic observational study with a cross-sectional approach conducted in AnatomicalPathology Institute of Dr. Soetomo Hospital, Surabaya that used 44 samples of paraffin blocks from radicalnephrectomy preparations for CCRCC patients at the period of January 2013-December 2018, which weredivided based on perirenal fat invasion status. The analyzed was using Spearman test. EMMPRIN expressionis positively correlated with perirenal fat invasiveness (p = 0.019) in clear cell renal cell carcinoma.EMMPRIN expression is related with perirenal fat invasiveness, in clear cell renal cell carcinoma.

Mimicker of Renal Cell Carcinoma- A Case Report

Oncocytoma is a rare epithelial tumour composed of oncocytes which are epithelial cells with excessive amount of mitochondria. The tumour is most often benign, and diagnosis can be made on the basis of histopathological examination. Here, the authors present a 64-year-old female patient, with complaints of abdominal discomfort and flank pain, along with history of loss of weight and appetite for one month. Radiology showed a left renal mass of measuring 9×7×4.5 cm involving the upper and middle pole suggestive of malignancy. Following which radical nephrectomy was done. Examination of gross specimen showed a fairly circumscribed brownish lesion in the upper and middle pole of left kidney measuring 8.8×7×4.5 cm with a central scar. There was no evidence of hilar and perirenal fat invasion. Histology showed sheets of large polygonal eosinophilic cells with centrally placed nucleus. The differentials were eosinophilic variant of clear cell renal cell carcinoma, chromophobe renal cell carcinoma and oncocytoma. A panel of Immunohistochemical (IHC) markers was performed for further categorisation and the lesional cells were positive for CD 117 and negative for CD 7 and CD 10. This ruled out the differentials and confirmed oncocytoma, thus ruling out the necessity for chemotherapy.

Clinical Significance of Tumor Size, Pathological Invasion Sites Including Urinary Collecting System and Clinically Detected Renal Vein Thrombus as Predictors for Recurrence in pT3a Localized Renal Cell Carcinoma.

The recent eighth tumor-node-metastasis (TMN) staging system classifies renal cell carcinoma (RCC) with perirenal fat invasion (PFI), renal sinus fat invasion (SFI), or renal vein invasion (RVI) as stage pT3a. However, limited data are available on whether these sites have similar prognostic value or recurrence rate. We investigated the recurrence rate based on tumor size, pathological invasion sites including urinary collecting system invasion (UCSI), and clinically detected renal vein thrombus (cd-RVT) with pT3aN0M0 RCC. We retrospectively reviewed 91 patients with pT3aN0M0 RCC who underwent surgical treatment. Patients with tumor size > 7 cm, UCSI, three invasive sites (PFI + SFI + RVI), and cd-RVT showed a significant correlation with high recurrence rates (hazard ration (HR) 2.98, p = 0.013; HR 8.86, p < 0.0001; HR 14.28, p = 0.0008; and HR 4.08, p = 0.0074, respectively). In the multivariate analysis, tumor size of >7 cm, the presence of UCSI, and cd-RVT were the independent predictors of recurrence (HR 3.39, p = 0.043, HR 7.31, p = 0.01, HR 5.06, p = 0.018, respectively). In pT3a RCC, tumor size (7 cm cut-off), UCSI, and cd-RVT may help to provide an early diagnosis of recurrence.

Multiple Patterns of Perirenal Fat Invasion Are Associated With a Poorer Prognosis Compared With Isolated Invasion: A Proposal for a Revision of T3aN0M0 TNM Staging System.

Objectives: Currently, renal cell carcinoma (RCC) presenting with perisinus fat invasion (PSI) and/or perinephric fat invasion (PFI) is merged as one entity, pathological T3a (pT3a); however, the combination of PFI and PSI (PFI+PSI) may not be associated with equivalent prognosis compared with either PFI or PSI alone (PFI/PSI). Here, we analyzed the prognostic significance of PFI+PSI vs. PFI/PSI in pT3aN0–1M0–1 RCC.Method: We identified 5,290 patients with pT3aN0–1M0–1 RCC, treated by nephrectomy, from the Surveillance, Epidemiology and End Results database, between 2010 and 2016. Cox proportional hazards regression and Fine and Gray competing risks regression were fitted to assess risks of survival outcomes, respectively. 1:1 propensity score method was used to minimize differences in the covariates' distributions.Results: Among all patients, 746 patients (14.1%), 2,569 patients (48.5%) and 1,975 patients (37.3%) experienced PFI+SI, PFI, and PSI, respectively, and 3,952 patients (74.7%) without diseases of lymphnode (N1) and/or distant metastasis (M1). PFI alone compared with PSI alone showed a comparable overall survival (OS) and cancer-special survival (CSS), either PFI or PSI alone experienced a better OS and CSS than PFI+PSI. In patients with pT3aN0M0 RCC, PFI+PSI compared with the PFI/PSI was significantly associated with worse OS with hazard ratio (HR) [95% confidence interval (CI)]: 1.38 [1.12–1.69], p = 0.002 and 1.41 [1.06–1.87], p = 0.017 for unmatched data and matched data, respectively, and higher RCC-special mortality (HR [95%CI]: 1.55 [1.21–1.99], p = 0.001 and 1.70 [1.19–2.43], p = 0.004 for unmatched data and matched data, respectively). However, in pT3aN1/M1 RCC patients, PFI+PSI was not significantly associated with RCC-special mortality (HR [95%CI]: 1.02 [0.85–1.23], p = 0.800 and 0.99 [0.79–1.24], p = 0.920 for unmatched data and matched data, respectively) in comparison with PFI/PSI. In addition, invasion type was not an independent risk factor for patient's prognostication in the pT3a RCC with diseases of N1 and/or M1 (all p > 0.5).Conclusion: Multiple invasion patterns (PFI+PSI) are associated with inferior survival relative to PFI/PSI alone in patients with pT3aN0M0 RCC; however, these effects are masked in patients with metastatic disease. These results warrant consideration in the development of the next edition of the tumor-node-metastasis staging system, to improve risk stratification.

Predictors of Survival Outcomes in Non-Metastatic Renal Cell Carcinoma in Latin America and Spain: A Multicentric Analysis

Background: Renal cell carcinoma (RCC) is a lethal neoplasia. Data from Latin America are scarce, and the distinct ethnic origins of this population could affect predictive or prognostic factors. Objective: We aim to describe a large cohort of non-metastatic renal cell carcinoma, identifying the demographic, clinical, and pathological prognostic factors for survival. Methods: We used a multi-institutional retrospective cohort involving 5,670 patients who underwent radical or partial nephrectomy across seven Latin American countries and Spain from 1980 to 2016. The variables were compared, and Kaplan–Meier curves were used to estimate the overall survival (OS) and cancer-specific survival (CSS). Results: The clear cell subtype represented 66.7% of RCC, followed by chromophobe (13.7%), papillary (5.2%), and others (14.4%). Furthermore, 72.3% of renal masses were &lt;7.0 cm. The 5-year OS and 10-year OS rates were 86.1% and 69.5%, respectively. The 5-year and 10-year CSS rates were 89.9% and 81.8%, respectively. The demographic and clinical predicting factors for OS in the multivariate analysis were age (HR: 2.978), anemia (HR: 1.44), presence of symptoms at presentation (HR: 1.26), Karnofsky score ≤80 (HR: 2.12), and ASA score ≥ 3 (HR: 1.49). The pathological factors were nodal metastasis (HR: 2.14), peri-renal fat invasion (HR: 2.12), inferior vena cava invasion (HR: 1.61), histologic tumoral necrosis (HR: 1.69), and tumor size &gt;7 cm (HR: 1.64). Conclusions: Our findings agreed with those reported for some developed countries. We emphasize that ASA and peri-renal fat invasion as prognostic factors deserve further study. Information regarding microvascular invasion should be regularly incorporated in pathological reports.

Risk Factors for Upstaging, Recurrence, and Mortality in Clinical T1-2 Renal Cell Carcinoma Patients Upstaged to pT3a Disease: An International Analysis Utilizing the 8th Edition of the Tumor-Node-Metastasis Staging Criteria

To investigate risk factors for and outcomes in pathological T3a-upstaging in Renal Cell Carcinoma (RCC), as Tumor-Node-Metastasis staging for T3a RCC was recently revised. Multicenter retrospective analysis of patients with clinical T1-T2 RCC, stratified by occurrence of pathologic T3a-upstaging. Primary outcome was recurrence-free survival (RFS). Multivariable analyses (MVA) were conducted for upstaging and recurrence. Kaplan-Meier analysis (KMA) was utilized for RFS and overall survival (OS). We analyzed 2573 patients (1223 RN/1350 PN). Upstaging occurred in 360 (14.0%). On MVA, higher clinical stage was associated with increasing risk of upstaging [cT1a (referent), odds ratio for cT1b, cT2a, and cT2b was 2.6, 6.5, and 14.1, P < .001]. Higher clinical stage at presentation correlated with increasing risk of recurrence in pT3a-upstaged RCC (cT1a upstaged-pT3a [referent], hazard ratio [HR] for cT1b, cT2a, and cT2b upstaged pT3a was 1.16 [P=.729], 3.02 [P=.013], and 4.5 [P=.003]). Perirenal fat (HR 1.6, P=.038) and renal vein (HR 2.2, P=.006) invasion were associated with increased risk of recurrence; type of surgery was not (P=.157). KMA for RFS and OS in pT3a-upstaged patients demonstrated differences based on initial clinical stage (5-year PFS for cT1a/b, and cT2 upstaged was 84.5%/72.8%, and 44.7%, P < .001; 5-year OS for cT1 and cT2 upstaged was 83.8% and 63.2%, P < .001). Risk of pT3a-upstaging and recurrence in pT3a-upstaged RCC correlates with clinical stage at presentation. Renal vein and perinephric fat invasion were associated with increased risk of recurrence. PN did not increase risk of recurrence and potential of pT3a-upstaging should not deter consideration of PN.