Natural history and growth kinetics of clear cell renal cell carcinoma in sporadic and von Hippel-Lindau disease

BackgroundTo evaluate and compare the natural history and growth kinetics of sporadic clear cell renal cell carcinoma (ccRCC) with those of ccRCC in von Hippel-Lindau disease (VHL).MethodsSixty patients in the sporadic group with 61 tumors and 15 patients in the VHL group with 30 tumors whom all underwent delayed surgery after at least 12 months of active surveillance (AS) were enrolled to conduct a retrospective cohort study. The growth rate was calculated, and the growth kinetics between the sporadic and VHL groups were compared. The patient and tumor characteristics were reviewed, and their correlation with growth rate was analyzed.ResultsThe mean growth rate of sporadic ccRCC was 0.91 cm/year (ranging from 0–4.74 cm/year) and that of VHL ccRCC was 0.47 cm/year (ranging from 0.04–1.89 cm/year). The growth rate of sporadic ccRCC showed a tendency of being faster than that of VHL ccRCC but did not reach statistical significance (P=0.07). The factors affecting the growth rate were different between the two groups. For VHL ccRCC, the only factor that correlated with growth rate was initial tumor diameter (P<0.001), but for sporadic ccRCC, the only factor was pathological nuclear grade (P<0.001).ConclusionsThe growth rate of VHL-associated ccRCC might be slower than that of sporadic ccRCC. Furthermore, we identified a disparity in growth kinetics between sporadic and VHL-associated ccRCC.     

Assessment of the prognostic value of SPOCK1 in clear cell renal cell carcinoma: a bioinformatics analysis

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common urological malignancies, and once metastasis occurs, it often has a poor prognosis and lacks effective treatment. Therefore, there is an urgent need to screen some new biomarkers and explore their molecular mechanisms to improve the early clinical diagnosis and targeted therapy of ccRCC. SPOCK1 (SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1) is a conserved multi-domain proteoglycan that plays an important role in the development of multiple cancer types; however, its prognostic value in ccRCC has not been investigated. The study of the prognostic value of SPOCK1 in ccRCC is a good complement to the study of ccRCC biomarkers.MethodsDatabases of this study included Oncomine, Kaplan-Meier Plotter, GEPIA, GeneMANIA, cBioPortal, and TIMER. Student’s t-test was used to analyze the differences in SPOCK1 expression in ccRCC tissues compared with tumor-adjacent normal tissues. Kaplan-Meier curves for survival analysis were used to assess the correlation between the expression of SPOCK1 and the prognostic outcomes. Correlation module drew the expression scatterplots between SPOCK1 and immune cell infiltration in ccRCC, together with the Spearman’s rho value and estimated statistical significance.ResultsThe SPOCK1 mRNA expression was significantly higher in ccRCC tissues (mean expression ± SD: 920.2±195.2) than in normal tissues (mean expression ± SD: 358.4±29.1, P=0.008), and high SPOCK1 expression significantly and positively correlated with the pathological stage of ccRCC patients (F value =10.2, P<0.001). Higher expression of SPOCK1 was also associated with significantly shorter overall survival (OS) and disease-free survival (DFS) in ccRCC patients (GEPIA: P=0.046, P<0.001, respectively; Kaplan-Meier Plotter: P=0.002, P=0.0022, respectively). The function of SPOCK1 is mainly related to tumor development and extracellular matrix remodeling, and it may participate in the epithelial-mesenchymal transition process. SPOCK1 expression significantly and positively correlated with infiltration of several immune cells in ccRCC, including cancer-associated fibroblasts (CAFs) (Rho =0.333, P=2.16×10⁻¹³), tumor-associated macrophages (TAMs) (Rho =0.18, P=1.02×10⁻⁴), and tumor-associated neutrophils (TANs) (Rho =0.165, P=3.83×10⁻⁴). Conversely, there was a significant and negative correlation between SPOCK1 expression and infiltration of CD4⁺ T cells (Rho =−0.113, P=0.015).ConclusionsSPOCK1 may be a potential prognostic biomarker in ccRCC.     

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

BackgroundAccurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.MethodsmRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).ResultsAmong 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16–58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26–1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27–1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23–1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24–1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16–1.99, P=0.002).ConclusionsIn our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.     

Prognostic significance of preoperative Naples prognostic score on short- and long-term outcomes after pancreatoduodenectomy for ampullary carcinoma

BackgroundThe Naples prognostic score (NPS) is an effective and objective tool to assess the immune–nutritional status of patients with malignant tumors. The aim of this study was to investigate the clinical significance of preoperative NPS on short- and long-term outcomes after pancreatoduodenectomy (PD) for ampullary carcinoma.MethodsWe retrospectively analyzed 404 consecutive patients with ampullary carcinoma who underwent PD between January 2012 and June 2018. Preoperative NPS was calculated from serum albumin and total cholesterol concentrations, and the neutrophil–lymphocyte ratio and lymphocyte-monocyte ratio (LMR). Patients were then divided into three groups according to their NPS. Clinicopathological variables, postoperative outcomes, and survival data were compared between the three groups. Univariate and multivariate Cox analysis of overall survival (OS) and recurrence-free survival (RFS) were also conducted, and time-dependent receiver operating characteristic (ROC) curves were created to evaluate the discriminatory ability of the prognostic scoring systems.ResultsPatients with higher NPS had worse prognosis, and significant OS difference (group 0 vs. 1, P=0.02; group 1 vs. 2, P<0.001; group 0 vs. 2, P<0.001) and RFS difference (group 0 vs. 1, P=0.088; group 1 vs. 2, P<0.001; group 0 vs. 2, P<0.001). Multivariate analysis revealed that NPS was an independent significant predictor of OS (grade 2 vs. grade 1 or 0, hazard ratio: 3.067; P<0.001) and RFS (grade 2 vs. grade 1 or 0, hazard ratio: 2.732; P<0.001). The time-dependent receiver operating curve analysis showed that NPS had better prognostic performance for OS and RFS than other prognostic models. Additionally, significant differences in the incidence of postoperative morbidity were observed between the three groups, and the NPS was an independent risk factor of overall postoperative complications (grade 2 vs. grade 1 or 0, odds ratio: 1.692; P=0.02).ConclusionsThe NPS was an independent predictor of overall- and RFS in patients undergoing PD for ampullary carcinoma, and was independently associated with the incidence of postoperative complications.     

术前中性粒细胞与淋巴细胞比值和血小板与淋巴细胞比值对肾透明细胞癌的预后评估价值

目的:探究术前外周血中性粒细胞与淋巴细胞比值(NLR)和血小板与淋巴细胞比值(PLR)在评估肾透明细胞癌(ccRCC)患者预后的作用。方法:回顾性分析2001年12月—2010年12月在我院接受手术治疗的352例肾细胞癌(RCC)患者的临床资料,年龄25~82岁,平均(55.1±12.2)岁;随访时间1~200个月,平均(106.1±35.1)个月;中位总生存期(OS)为104个月,中位无复发生存期(RFS)为101个月。通过受试者工作特征曲线(ROC)确定NLR及PLR的最佳临界值并进行分组,通过Kaplan-Meier法和Cox回归对RCC患者中的NLR及PLR进行预后分析。结果:按最佳临界值NLR<2.05(155例)及≥2.05(197例)、PLR<140(236例)及PLR≥140(116例)对患者进行分组。高NLR及PLR与大肿瘤直径(P=0.026,P=0.019)、高肿瘤TNM分期(P=0.003,P<0.001)、高肿瘤Fuhrman分级(P=0.021,P=0.008)及转移或复发有关(P<0.001,P<0.001)。相比于单独使用NLR或PLR,联合NLR及PLR能够更有效地预测OS及RFS。Cox多因素分析结果提示高NLR(P<0.001)、高PLR(P=0.004)、患者年龄≥60岁(P<0.001)、大肿瘤直径(P=0.043)、高肿瘤TNM分期(P<0.001)、高肿瘤Fuhrman分级(P<0.001)与患者OS相关,并且高NLR(P=0.012)、高PLR(P=0.014)、高肿瘤TNM分期(P<0.001)、高肿瘤Fuhrman分级(P=0.002)与患者RFS相关。结论:术前NLR及PLR是ccRCC患者术后OS及RFS的独立预后因素。高NLR、PLR预示着ccRCC患者较高的复发转移风险及较差的生存预后。     

肾透明细胞癌患者术前血清高敏C反应蛋白和降钙素原水平与肿瘤病理分期、分级的相关性研究

目的 探讨肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)患者术前血清高敏C反应蛋白(high sensitive C-reactive protein,hs-CRP)和降钙素原(procalcitonin,PCT)水平与肿瘤病理分期、分级的相关性.方法 采用ELISA对2014年9月至2016年9月内蒙古医科大学附属医院泌尿外科收治的行肾癌根治术或肾部分切除术的98例ccRCC患者术前血清hs-CRP与PCT水平进行检测,并分析其与肿瘤病理分期、分级的相关性.结果 与病理分期为pT1[0.610(0.006~2.730)mg/L]及pT2[0.990(0.140~3.120)mg/L]的患者相比较,pT3+4患者的血清hs-CRP水平增高[1.510(0.070~3.940)mg/L],差异有统计学意义(P<0.05);与Fuhrman分级为Grade1~2组患者相比较,Grade3~4组患者血清hs-CRP水平增高[0.270(0.005~2.690)vs1.410(0.130~3.880)mg/L],差异有统计学意义(P<0.05).与病理分期为pT1[0.060(0.001~2.630)ng/ml]组患者相比较,pT2[0.420(0.023~1.550)ng/ml]和pT3+4[0.480(0.080~2.630)ng/ml]组患者的血清PCT水平增高,差异有统计学意义(P<0.05);与Fuhrman分级为Grade1~2的患者[0.050(0.001~1.220)ng/ml]相比较,Grade3~4[0.270(0.013~2.800)ng/ml]的患者其血清PCT水平增高,差异有统计学意义(P<0.05).受试者工作曲线分析结果表明,血清hs-CRP水平的阈值为0.652mg/L(灵敏度94.7%、特异性83.0%),血清PCT水平的阈值为0.086ng/ml(灵敏度82.1%、特异性80.5%).结论 ccRCC患者术前hs-CRP和PCT水平与肿瘤的病理分期、分级具有相关性.     

Valor pronóstico de la invasión de grasa perirrenal y/o del seno en pacientes con carcinoma de células renales pT3a: estudio de cohorte multicéntrico. Grupo LARCG

Introduction and objectivesThe objective of this study is to evaluate overall survival (OS), cancer-specific survival (CSS), relapse-free survival, local and distant (LRFS and DRFS, respectively) rates in patients with pT3a renal cell carcinoma (RCC) considering the perirenal and/or sinus fat infiltration (FI) as prognostic factors.Materials and methodsRetrospective cohort of patients with pT3a RCC who underwent radical or partial nephrectomy. The data were extracted from the LARCG (Latin American Renal Cancer Group) database. The demographic, clinical, pathological and surgical variables were evaluated. FI was divided into 4 groups (vein, perirenal, sinus and both fats infiltration). The Kaplan Meier and Cox regression curves were performed.Results293 patients were included in the study. The mean age was 61.4 years. The median follow-up was 21 months (r: 1-194). CSS, RFS, LRFS and DRFS estimated at 3 years in the group of both fats’ infiltration were 53.1, 45.1, 58.7 and 51.6 months, respectively, and always statistically lower than the rest (P?0.005). In the multivariate analysis, the infiltration of both fats significantly increased specific mortality, overall and local relapse with respect to vein infiltration (HR: 4.5, 2.42 and 8.08, respectively). The Fuhrman grade and renal pelvis infiltration were independent predictors of CSS and RFS.ConclusionsInfiltration of both fats increases the risk of overall and local relapse in pT3a RCC. In the same way, it is associated with a lower cancer-specific survival and should be considered as a factor of poor prognosis.     

A meta-analysis for comparison of partial nephrectomy vs. radical nephrectomy in patients with pT3a renal cell carcinoma

BackgroundKidney cancer is the most common malignant tumor of the kidney in adults. However, in terms of the treatment for pT3a renal cell carcinoma (RCC), whether partial nephrectomy (PN) can be selected is still controversial. This study was conducted to compare the efficacy of PN and radical nephrectomy (RN) in treatment for patients with pT3a RCC.MethodsThe relative English databases including PubMed and EMBASE were searched for studies comparing PN and RN for pT3a RCC between 2010 and 2020. Stata 13.0 software was used to compare the cancer-specific survival (CSS), overall survival (OS), cancer-specific mortality (CSM), relapse-free survival (RFS), complications and positive surgical margin.ResultsNine articles were included with a total of 3,391 patients, of whom 2,113 received RN and 1,278 received PN. The results showed that there is no statistical difference in CSS, OS, CSM, RFS, complications and positive surgical margin between RN and PN. No heterogeneity was shown in study.ConclusionsThere were no differences in the CSS, OS, CSM, RFS, complications and positive surgical margin of the patients in RN and PN group. For pT3a RCC, RN did not provide a better survival benefit compared to PN. Considering PN can suppress the progression of tumor and reduce the risk of postoperative chronic renal insufficiency, we found PN is a good choice for pT3a RCC. However, further large-sample, studies are still needed in future.     

Grading Chromophobe Renal Cell Carcinoma: Evidence for a Four-tiered Classification Incorporating Coagulative Tumor Necrosis

BackgroundAlthough grading systems have been proposed for chromophobe renal cell carcinoma (ChRCC), including a three-tiered system by Paner et al (Paner GP, Amin MB, Alvarado-Cabrero I, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol 2010;34:1233–40), none have gained clinical acceptance, and the World Health Organization (WHO) currently recommends against grading ChRCC.ObjectiveTo validate a previously published grading scheme and propose a scheme that includes tumor necrosis.Design, setting, and participantsA total of 266 patients who underwent nephrectomy for nonmetastatic ChRCC between 1970 and 2012 were reviewed for ChRCC grade according to the Paner system and coagulative tumor necrosis.Outcome measurements and statistical analysisAssociations with cancer-specific survival (CSS) were evaluated using Cox proportional hazard regression models and summarized with hazard ratios (HRs).Results and limitationsTwenty-nine patients died from RCC; the median follow-up was 11.0 (interquartile range 7.9–15.9) yr. ChRCC grade according to the Paner system was significantly associated with CSS, including the difference in outcome between grade 1 and 2 tumors. Among patients with grade 2 tumors, the presence of tumor necrosis helped delineate patients with worse CSS. As such, the Paner system was expanded to four tiers separating grade 2 into those with and without tumor necrosis. HRs for associations of the proposed grade 2, 3, and 4 tumors with CSS were 4.63 (p = 0.007), 17.8 (p < 0.001), and 20.9 (p < 0.001), respectively. The study is limited by the lack of multivariable analysis including additional pathologic features.ConclusionsThe expansion of a previously reported ChRCC grading system from three to four tiers by the inclusion of tumor necrosis helps further delineate patient outcome and can, therefore, enhance patient counseling following surgery. It also aligns the number of ChRCC grades with the WHO/International Society of Urologic Pathology four-tiered grading systems for clear cell and papillary RCC.Patient summaryChromophobe renal cell carcinoma is the third most common type of renal cancer, and unlike other renal cancers, there is no accepted prognostic grading system. In this study, we found that a grading system that included a pathologic feature of tumor necrosis could better define outcomes for patients with chromophobe renal cell carcinoma.     

SMARCC1 expression is positively correlated with pathological grade and good prognosis in renal cell carcinoma

BackgroundRenal cell carcinoma (RCC), which is derived from the renal tubular epithelium, is now the most common urological cancer. Of the four RCC subtypes, clear cell RCC (ccRCC) is the most common subtype and accounts for 75–80% of all RCC cases. SMARCC1, also known as BAF155, together with SMARCA4, SMARCA2, and SMARCB1, comprises the SWI/SNF protein family. It has been reported that the expression of SMARCC1 was correlated with some human cancers including prostate cancer, colon cancer, and pancreatic cancer. However, the mechanisms and regulatory roles of SMARCC1 in ccRCC are not well defined.MethodsOur current study primarily investigated the expression of SMARCC1 and its clinical importance in two common histological types of ccRCC using microarrays (HKidE180Su02, MecDNA-HKidE030CS01).ResultsThe results showed that the expression of SMARCC1 in ccRCC tissues was significantly decreased compared with that in corresponding para-tumor tissue (4.370±2.036 vs. 6.167±1.162, P=0.001). SMARCC1 expression was positively correlated with pathological grade (r=0.224, P=0.011). Moreover, ccRCC patients with high SMARCC1 expression had a better prognosis than those with low SMARCC1 expression (40.0% vs. 95.2%, P=0.000) in the following sub-groups: pathological grade (III and IV), male sex (73.5% vs. 95.3%, P=0.004), and tumor size >5 cm (62.5% vs. 89.5%, P=0.044).ConclusionsA further study is necessary to explain the mechanism of the occurrence and progression of ccRCC.     

Tumor necrosis adds prognostically significant information to grade in clear cell renal cell carcinoma: A study of 842 consecutive cases from a single institution. Khor LY,Dhakal HP,Jia X,Reynolds JP,McKenney JK,Rini BI,Magi-Galluzzi C,Przybycin CG.Am J Surg Pathol. September 2016;40(9):1224–1231.

Tumor necrosis has been shown to be an independent predictor of adverse outcome in renal cell carcinoma. A modification of the International Society of Urological Pathology (ISUP) grading system for renal cell carcinomas has recently been proposed, which incorporates the presence of tumor necrosis into grade. The investigators proposing this system found that necrosis added significant prognostic information to ISUP grade. We attempted to describe our experience with the effect of tumor necrosis in relationship to nuclear grade by reviewing the slides from a large consecutive series of localized clear cell renal cell carcinomas from our institution and obtaining long-term clinical follow-up information (overall survival). Of the 842 clear cell renal cell carcinomas reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and 140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. A total of 547 (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%) were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2 months (range: 0.12–273.6), and 310 (36.8%) patients died. On univariable analysis, there was no significant difference in outcome for tumors of ISUP grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade 4 and necrosis were significant predictors of overall survival on multivariable analysis. When the recently proposed modified grading system incorporating tumor necrosis was applied to our data, there was no significant difference in overall survival between patients with modified grade 1 tumors and those with modified grade 2 tumors (P = 0.31); however, there was a statistically significant difference between patients with modified grade 1 or 2 tumors and those with modified grade 3 tumors (P = 0.04), and a substantial difference in outcome between those with modified grade 3 and modified grade 4 tumors (P<0.001). When a recursive partitioning approach was applied to our data, patients of a given ISUP grade could be further prognostically separated according to the presence or absence of necrosis and could be divided into 3 statistically significant prognostic groups: (1) non-necrotic ISUP grade 1 to 3 tumors, (2) ISUP grade 1 to 3 tumors with necrosis and ISUP grade 4 tumors with<10% necrosis, and (3) ISUP grade 4 tumors with>10% necrosis. In conclusion, our study shows that tumor necrosis adds additional prognostic information to ISUP grade and that quantification of necrosis can further stratify patients with ISUP grade 4 tumors.     

The prognostic value of the site of invasion in T3aN0M0 clear cell renal cell carcinoma

Background

The 7th Tumor-Node-Metastasis system for clear cell renal cell carcinoma (ccRCC) classified renal sinus fat invasion (SFI), perirenal fat invasion (PFI), or renal vein invasion (RVI) as stage pT3a. However, their close interactions and prognostic value of them remain controversial. The goal of this study is to further analyze their prognostic values for patients with T3aN0M0 ccRCC.

Tumor VEGF expression correlates with tumor stage and identifies prognostically different groups in patients with clear cell renal cell carcinoma

ObjectivesVascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis and represents the key element in the pathogenesis of clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the use of tumor VEGF expression as a parameter to identify tumor stage and prognostically different patient groups.Methods and materialsWe retrospectively collected clinical data of 137 patients treated with partial or radical nephrectomy at our institutions for organ-confined, locally advanced, and metastatic ccRCCs between 1984 and 2013. Tumor cell VEGF immunohistochemical expression was compared with pathological and clinical features including age, sex, tumor stage, and Fuhrman grade. Comparison of VEGF expression levels between tumor stages was performed via Kruskal-Wallis nonparametric test. Survival analysis was conducted via Kaplan-Meier product-limit method, and Mantel-Haenszel log-rank test was employed to compare survival among groups.ResultsMedian age at diagnosis was 61 years (range: 33–85 y). Tumor stage was pT1N0M0 in 67 patients (49%), pT2N0M0 in 5 (4%), and pT3N0M0 in 25 (18%), while 40 patients (29%) had metastatic tumors at diagnosis. Fuhrman nuclear grade was G1 in 22 patients (16%), G2 in 60 (44%), G3 in 33 (24%), G4 in 13 patients (9%), and unknown in 9 patients. Tumor VEGF was differentially expressed among different stages (P<0.001) and in low (G1–2) and high (G3–4) Fuhrman grade tumors (P<0.001). No significant differences were found when stratifying by sex (P = 0.06) or age (P = 0.29). Median overall survival (OS) from partial or radical nephrectomy was 161 months (range: 1–366). We observed a significantly longer OS in patients with low (<25%) vs. high (>25%) VEGF expression levels (median OS 206 vs. 65 mo, P<0.001).ConclusionsOur data show that tumor cell VEGF expression is significantly associated with tumor stage and Fuhrman grade and is able to predict patient outcome, suggesting a potential use of this parameter in identifying prognostically different patients with ccRCC.     

Prognostic value of peripheral blood T lymphocyte subsets in clear cell renal cell carcinoma

BackgroundTo date, few studies have evaluated the role of peripheral blood T lymphocyte subsets in patients with clear cell renal cell carcinoma (ccRCC). Here we measured the levels of peripheral blood T lymphocyte subsets and evaluated its prognostic value in ccRCC.MethodsData from 122 patients with RCC from January 2018 to January 2020 were collected. Preoperative peripheral blood T lymphocyte subsets and medical records were analyzed. Kaplan-Meier cures and log rank test were used for analyzing overall survival (OS). Univariate and multivariate survival analyses were underwent by performing the Cox proportional hazards models. Correlations were tested by Pearson’s correlation analysis.ResultsOf 122 patients, a total of 80 ccRCC patients was enrolled. Patients with low CD3⁺ T cells and low CD4⁺/CD8⁺ ratio displayed a worse OS than patients with high CD3⁺ T cells and high CD4⁺/CD8⁺ ratio (P=0.029 and 0.002, respectively). Multivariate analyses showed CD3⁺ T cells and CD4⁺/CD8⁺ ratio were independent predictive factors for the OS (HR: 0.295, 95% CI, 0.091–0.956; P=0.042 and HR: 0.244, 95% CI, 0.065–0.920; P=0.037, respectively). Moreover, NLR negatively correlated with both levels of CD3⁺ T cells and CD4⁺/CD8⁺ ratio (P<0.001, r=−0.398 and P=0.012, r=−0.280, respectively).ConclusionsThe findings of our study suggest that preoperative CD3⁺ T cells and CD4⁺/CD8⁺ ratio in peripheral blood are independent predictors for patients with ccRCC.     

Leibovich score is the optimal clinico-pathological system associated with recurrence of non-metastatic clear cell renal cell carcinoma

PurposeTo determine the optimal post-operative risk stratification system associated with survival following surgery for clear cell renal cell carcinoma (ccRCC): tumour grade, tumour stage, Leibovich 2003, Leibovich 2018, Kattan, Stage, size, grade and necrosis (SSIGN) or UCLA Integrated Staging System (UISS) scores.Methods542 patients with non-metastatic ccRCC who underwent nephrectomy 2008?2018 were reviewed. Primary outcome was recurrence-free survival (RFS), with secondary outcomes cancer-specific survival (CSS) and overall survival (OS).ResultsAll systems were significantly associated with RFS, CSS and OS by Kaplan-Meier and unadjusted Cox-regression. ROC analysis identified that Leibovich 2003, Leibovich 2018A or B and SSIGN were optimally association with 5year RFS (AUC (Area under curve) 0.87, 0.86, 0.86 and 0.86), but Leibovich 2003 or 2018A offered additional information on adjusted regression analysis (HR 1.24, P = 0.02; HR 1.17, P = 0.04). ROC analysis identified that Leibovich 2018B, Leibovich 2003, SSIGN and UISS were equally associated with 5 year OS (AUC 0.76, 0.74, 0.73 and 0.72). UISS added additional explanation of the variance in OS on adjusted regression analysis (HR 1.96, P = 0.002). A novel combination of Leibovich 2003 score and Eastern Co-operative Oncology Group (ECOG) performance status improved 5 year OS association compared to the Leibovich 2003 alone (AUC 0.78, P = 0.001), without affecting association with 5year RFS (AUC 0.87, P = 0.75).ConclusionsAll systems were robust tools associated with RFS, CSS and OS in ccRCC. In our cohort, the Leibovich 2003 and Leibovich 2018A scores may be better associated with RFS compared to other strategies. The UISS, Leibovich 2018B or Leibovich 2003 combined with ECOG performance status may stratify OS better than other modalities.     

Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.MethodsA total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27–78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.ResultsA total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0–28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III–IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III–IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414).ConclusionsThe most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III–IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I–II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.     

p21-Activated kinase 4 predicts early recurrence and poor survival in patients with nonmetastatic clear cell renal cell carcinoma

Backgroundp21-Activated kinase 4 (PAK4), a serine/threonine kinase implicated in the cytoskeleton organization to orchestrate cell morphology, adhesion, and motility, is associated with angiogenesis and vessel branching, which are important events in the progression of clear cell renal cell carcinoma (ccRCC). We investigated the effect of PAK4 expression on recurrence and survival among patients with nonmetastatic ccRCC following surgery.MethodsPAK4 expression was assessed, using immunohistochemistry, in 376 patients with nonmetastatic ccRCC after nephrectomy, where data of 187 patients were obtained from 2013 to 2014 and of 189 patients were obtained from 2008. Kaplan-Meier and Cox regression analyses were used to associate PAK4 expression with overall survival and recurrence-free survival.ResultsOverall, 41.2% and 36.5% of specimens exhibited high PAK4 expression in 2 cohorts. Patients with high PAK4 expression were prone to possess high Fuhrman grade and tumor necrosis. Moreover, high PAK4 intensity was significantly associated with poor overall survival and recurrence-free survival. PAK4 expression remained an independent adverse prognosticator after adjusting for other well-established factors. Furthermore, in subgroups stratified by Fuhrman grade or T category, patients with high PAK4 intensity had an increased risk of recurrence and death. After adjusting for age, high PAK4 expression was an adverse prognostic marker in subgroup of low Fuhrman grade and in subgroup of early T category.ConclusionPAK4 expression is an independent adverse prognostic biomarker for recurrence and survival among patients with low-risk ccRCC after nephrectomy.     

Propensity-matched pair analysis of safety and efficacy between laparoscopic and open radical nephrectomy for the treatment of large renal masses (>10 cm): a retrospective cohort study

BackgroundOpen radical nephrectomy (ORN) is a practical procedure for treating patients with large renal carcinomas >10 cm in size, and few studies have focused on feasibility and safety of laparoscopic radical nephrectomy (LRN). The current study was to assess the safety and effectiveness of LRN and ORN in large renal carcinoma patients by propensity matched pair analysis.MethodsIn this cohort study, a retrospective review of radical nephrectomy data from October 2010 to October 2018 at Changhai Hospital was conducted. Patients with renal carcinomas >10 cm in size by pre-operative images were included. Patients’ demographics including age, gender, body mass index (BMI), tumor size, operation time, hospitalization days, etc. were collected. Renal tumor patients undergoing LRN or ORN were match-paired by gender, BMI, age, and tumor size. Peri-operative outcomes including estimated blood loss and complications were compared. The follow-up contents included survival time, disease progression, and cause of death, and cancer-specific and progression-free survival were estimated via Kaplan-Meier curve analysis.ResultsAmong 92 patients with clinical T2b renal masses, 37 pairs were matched. The average tumor sizes of the LRN and ORN groups were 11.37±0.30 and 11.67±0.33 cm (P=0.375), respectively. The average operating time for LRN was slightly longer (204.32±11.17 vs. 192.78±8.50 min, P=0.414). Estimated blood loss (EBL) (336.49±63.58 mL for LRN vs. 545.95±74.52 mL for ORN, P=0.036), the length of postoperative stay [6.0 (5.0–9.0) for LRN vs. 9.0 (6.0–11.5) days for ORN, P=0.015], and removal time of the drainage tube [4.0 (3.0–5.0) days for LRN vs. 5.0 (4.0–6.0) for ORN, P<0.001] were less than in the LRN group. The pathological subtype and Fuhrman grade were comparable. Both groups were followed up for a similar period, and no difference was observed in 5-year survival rates.ConclusionsConsidering the conversion rates and overall complication rates, it seems that LRN for large renal carcinomas demonstrated equivalent peri-operative safety and effectiveness compared with ORN, with no adverse effects on midterm oncological outcomes.     

Systematic sampling during MRI-US fusion prostate biopsy can overcome errors of targeting—prospective single center experience after 300 cases in first biopsy setting

BackgroundMultiparametric magnetic resonance imaging (mpMRI) and targeted biopsy have become an integral part of the diagnosis of prostate cancer (PCa), as recommended by the European Association of Urology Guidelines. The aim of the current study was to evaluate the performance of MRI and MRI-transrectal ultrasound (TRUS) fusion prostate biopsy as first biopsy setting in a tertiary center.MethodsA cohort of 300 patients was included in the current analysis. All patients presented with clinical or biochemical suspicion of PCa and harbored at least one suspect lesion on mpMRI. MRI-TRUS fusion prostate biopsy, followed by 12 core systematic prostate biopsy were performed by the same operator using a rigid registration system.ResultsThe mean age of the patients was 64 years (IQR: 58–68.5 years) and the mean PSA was 6.35 ng/mL (IQR: 4.84–9.46 ng/mL). Overall cancer and csPCa diagnosis rates were 47% and 40.66%. Overall PCa/csPCa detection rates were 20.4%/11.1%, 52%/45% and 68.5%/66.7% for PI-RADS lesions 3, 4 and 5 (P<0.001/P<0.0001). Larger lesion diameter and lesion volume were associated with PCa diagnosis (P=0.006 and P=0.001, respectively). MRI-TRUS fusion biopsy missed PCa diagnosis in 37 cases (of whom 48.6% ISUP 1) in comparison with 9 patients missed by systematic biopsy (of whom 11.1% ISUP 1). In terms of csPCa, systematic biopsy missed 77.7% of the tumors located in the anterior and transitional areas. The rate of csPCa was highest when targeted biopsy was associated with systematic biopsy: 86.52% vs. 68.79% for targeted biopsy vs. 80.14% for systematic biopsy, P=0.0004. In 60.6% of cases, systematic biopsy was positive for PCa at the same site as the targeted lesion. Of these patients, eight harbored csPCa and were diagnosed exclusively on systematic biopsy.ConclusionsMRI-TRUS fusion prostate biopsy improves the diagnosis of csPCa. The main advantage of an MRI-guided approach is the diagnosis of anterior and transitional area tumors. The best results in terms of csPCa diagnosis are obtained by the combination of MRI-TRUS fusion with systematic biopsy. The systematic biopsy performed during MRI-targeted biopsy could have an important role in overcoming errors of MRI-TRUS fusion systems.     

Comparison of WHO 1973, WHO/ISUP 1998, WHO 1999 grade and combined scoring systems in evaluation of bladder carcinoma

OBJECTIVES: To compare WHO 1973, WHO/ISUP 1998 and WHO 1999 histologic grading systems, and also to evaluate the primary (most common) and secondary (second most common) patterns of cancer growth according to these three grading systems. MATERIAL AND METHODS: The study consisted of 87 bladder transurethral resections that were classified as grade 1, 2 and 3, and papillary urothelial neoplasm of low malignant potential (PUNLMP), low grade (LG) and high grade (HG) carcinoma considering WHO 1973 and WHO/ISUP, respectively. The WHO 1999 system was subdivided high grade into grades 2 and 3 (HG-2 and HG-3). For combined scoring, primary (most common) and secondary (second most common) grades according to extension were recorded for three grading systems. The number was repeated when only grade was seen in all extension of the tissue examined. A final combined score was obtained which ranged from 2 to 6 for the WHO 1973 and WHO/ISUP 1998 systems and from 2 to 8 for the WHO 1999 schema. The TNM system was used for the pathologic staging. RESULTS: When considering the pathological stage, there were statistical differences between the WHO 1973 grades (p=0.011 and p=0.000), and LG and HG carcinomas of WHO/ISUP 1998 (p=0.000) and also the WHO 1999 grades (p=0.010 and p=0.003), except PUNLMP. Regarding the combined scoring, significant differences were found between score 4 (2+2) and 5 (2+3) of WHO 1973 (p=0.014) and score 5 (LG+HG) and 6 (HG+HG) of WHO/ISUP 1998 (p=0.011). There was also a significant difference between scores 4 and 6, and 6 and 8 of the WHO 1999 combined scoring system (p=0.019 and p=0.019). WHO 1973, WHO/ISUP 1998 and WHO 1999 systems were positively correlated with the pathological stage (r(s)=0.30, r(s)=0.52 and r(s)=0.50, respectively), whereas there was weak association between the combined scoring systems and stage (r(s)=0.20, r(s)=0.18 and r(s)=0.19). Comparing these grading systems, the grade 2 of WHO 1973 was subdivided into LG and HG in WHO/ISUP 1998 and also LG-1and HG-2 in WHO 1999 systems. The group of HG carcinoma in WHO/ISUP 1998 which was subdivided into HG-2 and HG-3 in the WHO 1999 system was different statistically in relation to the stage. CONCLUSIONS: Our results revealed that the WHO 1999 system may be more useful to evaluate the bladder carcinoma histopathologically in comparison to the WHO 1973 and WHO/ISUP 1998 systems.