Microscopic venous invasion in renal cell carcinoma as a predictor of recurrence after radical surgery

BACKGROUND: The objective of the present study was to investigate the significance of microscopic venous invasion (MVI) as a prognostic factor for patients with renal cell carcinoma (RCC) who underwent radical surgery. METHODS: The study included a total of 157 consecutive patients with non-metastatic RCC who underwent radical surgery between January 1986 and December 2002. The median follow-up period was 45 months (range 6-162 months). Microscopic venous invasion was defined by the presence of a cancer cell in blood vessels based on the examination of hematoxylin-eosin stained specimens. Other prognostic variables were assessed by multivariate analysis to determine whether there was a significant impact on cancer-specific and recurrence-free survivals. RESULTS: Microscopic venous invasion was found in 70 patients, and of this number, 17 (24.7%) developed a tumor recurrence and 12 (17.1%) died of cancer progression, while only six (6.9%) of the remaining 87 patients without MVI presented with disease-recurrence and three (3.5%) died of cancer. Among the factors examined, the presence of MVI was significantly associated with age, mode of detection, tumor size, pathological stage and tumor grade; however, only pathological stage was an independent predictor for disease-recurrence, and none of these factors were available to predict cancer-specific survival in multivariate analyses. In 120 patients with pT1 or pT2 disease, MVI was noted in 36 patients. In this subgroup, recurrence-free survival rates in patients with MVI were significantly lower than those in patients without MVI, and MVI was the only independent prognostic predictor for disease-recurrence in a multivariate analysis. CONCLUSION: Microscopic venous invasion is not an independent prognostic factor in patients with non-metastatic RCC who underwent radical surgery; however, it could be the only independent predictor of disease-recurrence after radical surgery for patients with pT1 or pT2 disease.     

Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma

OBJECTIVE

To clarify the significance of microvessel density (MVD) in a retrospective investigation the relationship between the pattern of MVD (reflecting angiogenesis), and tumour stage, grade, size, and occurrence of microvessel invasion (MVI), metastasis, and cancer‐specific survival (CSS) in patients who had surgery for renal cell carcinoma (RCC).

PATIENTS AND METHODS

Vessels were labelled in sections of formalin‐fixed, paraffin‐embedded tissues from 54 RCCs by CD34 immunohistochemistry. The mean MVD, expressed as the number of vessels per 10 high‐power fields (HPF, ×400) were measured for each case. In addition, all pathological slides were reviewed for the presence and absence of MVI. The prognostic value of MVD and MVI was then evaluated, and correlated with the usual prognostic variables, tumour metastasis and CSS.

RESULTS

In a univariate analysis of CSS, the MDV tended to be lower as stage increased from pT1 to pT3, and as grade increased from G1 to G4, although it was statistically significant only for stage (P < 0.001 and 0.050, respectively). The mean MVD was higher in 42 nonmetastatic than in 12 metastatic tumours, and in 33 tumours associated with MVI than in 21 with no MVI (P < 0.001). The mean MVD was also lower and significantly different for 28 large than 26 small tumours (P = 0.005). The survival rate of patients with tumours that were small, low‐stage, of higher MVD, with no MVI and metastasis was significantly higher than that of patients with large, high‐stage, low MVD, with MVI and metastatic tumours (all P < 0.001). MVI was significantly more common with a decreasing trend in MVD and the presence of metastasis (Spearman rank correlation r_s = ?0.68, P = 0.01, and r_s = 0.39, P = 0.01, respectively). Independent prognostic factors in a multivariate analysis were: in all patients with RCC, tumour stage (P = 0.013) and metastasis (P = 0.028); in those with low MVD, MVI (P = 0.004) and metastases (P = 0.016); in those with no MVI, stage (P = 0.020); in those with MVI, MVD (P = 0.001); in those with no metastases, stage (P = 0.045); and in those with metastases, MVD (P < 0.001). No independent predictor was identified in patients with high MVD. In patients with no metastases there was a significantly shorter median CSS time in RCCs with low MVD and with MVI (P = 0.004 for both). Similarly, patients who had grade 3–4 tumours, vs those with lower MVD and with MVI, had a significantly shorter median CSS (P = 0.020 for MVD, and 0.01 for MVI).

CONCLUSIONS

This study suggested that MVD in RCC was inversely associated with MVI, tumour metastasis, patient survival and tumour diameter and stage, from the usual prognostic variables, but MVD was not an independent prognostic factor in multivariate analysis for all patients with RCC. Low MVD and the presence of MVI appears to be a marker for identifying patients with an adverse prognosis.     

Impact of renal vein invasion and fat invasion in pT3a renal cell carcinoma

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The presence of invasion of renal vein and perinephric fat are predictors of poor outcome in patients with RCC. The latest version of the TNM system included tumours exhibiting such parameters in the T3a stage, thus grouping tumours with distinct pathologic features. Our study showed that patients with RCC presenting concomitant invasion of the renal vein invasion and perinephric fat invasion have significantly worse survival rates than those showing any of the parameters separately. Therefore, we conclude that these tumours should not be grouped within T3a stage since they have significantly different outcomes.

OBJECTIVE

? To evaluate the prognostic impact of tumor fat invasion (FI) and renal vein invasion (RVI) in patients with T3a renal cell carcinoma.

PATIENTS AND METHODS

? In total, 220 consecutive patients treated for renal cell carcinoma between 1992 and 2009 were analyzed. T3a stage cases were selected. ? A single pathologist reviewed all cases.

RESULTS

? The present study cohort included 46 patients with mean follow‐up of 28.6 months, of whom 17 (36.9%) died from disease. Patients were initially divided into three groups including 24 (52.1%) of FI only, 11 (23.9%) of RVI only and 11 (23.9%) of both FI and RVI. ? In univariate analysis, no significant differences in disease‐specific survival (DSS) were noted between FI only and RVI only groups (P= 0.91). DSS was significantly worse in the FI + RVI group compared to the other groups (P= 0.02). ? When grouped into FI or RVI vs FI + RVI, DSS remained significantly lower in the group containing the parameters concurrently (P= 0.009). Progression‐free survival also was significantly lower in FI + RVI group (P= 0.01). ? Metastasis, positive lymph nodes and the presence of FI + RVI remained as isolated predictors of survival. ? Patients with FI + RVI presented a 2.6‐fold increase in risk of death from cancer and a 2.5‐fold increase in risk of disease progression (P= 0.04) compared to those with either of them alone.

CONCLUSION

? The isolated or concomitant presence of FI and RVI may be used as one of the criteria for staging in the next edition of the Tumour‐Node‐Metastasis classification because they have significantly different outcomes.     

NNMT在肾透明细胞癌的表达及对肾癌细胞侵袭能力的影响

目的:研究NNMT在肾透明细胞癌中的表达情况及对肾癌细胞侵袭能力的影响。方法:采用RT-PCR和Western blot方法检测正常肾小管上皮细胞株HKC、肾癌细胞株786-O及30例肾透明细胞癌组织、相应癌旁组织中NNMT的mRNA和蛋白的表达水平,并分析NNMT的mRNA水平与临床病理参数的关系。化学合成针对NNMT特异的siRNA序列,应用脂质体Lipofectamine 2000将其转染进786-O细胞中,利用RT-PCR和Western blot法检测NNMT在786-O细胞中的表达水平,用Transwell小室法检测肾癌细胞786-O侵袭能力的变化。结果:NNMT在肾癌细胞786-O中的mRNA和蛋白表达水平显著高于正常肾小管上皮细胞株HKC(P<0.001);肾透明细胞癌组织和对应的癌旁组织中NNMT的mRNA相对表达量分别为(1.582±0.2145)、(0.1269±0.04279),两组比较P<0.001。NNMT的mRNA水平与肿瘤大小、临床分期有关(P<0.05);Tran-swell法检测结果显示降低NNMT的表达后786-O细胞的侵袭能力明显下降。结论:NNMT在肾透明细胞癌组织和细胞中表达升高,可能在肾癌发生、发展过程中发挥重要作用。     

The extent of tumour fat invasion affects survival in patients with renal cell carcinoma and venous tumour thrombosis

Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Several studies have investigated the role of renal fat invasion in RCC with neoplastic thrombus. Our study confirmed that the simultaneous presence of TFI and VTT was associated with higher risk of CSM than the presence of VTT alone. We demonstrated for the first time that patients with either PFI or RSFI had a two‐fold increased risk of CSM compared with patients with VTT alone. Moreover, the combination of PFI and RSFI was associated with a three‐fold risk of CSM.

OBJECTIVE

? To investigate the effect of presence and extent of tumour fat invasion (TFI) – perinephric invasion (PFI), renal sinus fat invasion (RSFI) or both PFI and RSFI – on cancer‐specific mortality (CSM) in patients with renal cell carcinoma (RCC) and venous tumour thrombus (VTT).

METHODS

? We examined 184 consecutive patients with RCC with VTT treated with nephrectomy between 1987 and 2007. Associations with CSM were evaluated by univariable and multivariable Cox proportional hazard models.

RESULTS

? Median follow up was 21 months. The 5‐year CSM‐free survival estimates were 75%, 36% and 20% in patients with VTT without TFI, those with VTT with PFI or RSFI, and those with VTT with both PFI and RSFI, respectively (P < 0.001). In multivariable analyses, presence of either PFI or RSFI was associated with a two‐fold increased risk of CSM, whereas presence of both PFI and RSFI was associated with a three‐fold increased risk of CSM, relative to VTT‐only cases. ? The inclusion of the variable describing the presence and extent of TFI in a base model including pT stage, Fuhrman grade and presence of nodal disease and metastatic disease significantly increased the accuracy in predicting CSM (+2.1%; P < 0.001) in patients with VTT.

CONCLUSIONS

? Patients affected by RCC with VTT and TFI have a higher risk of CSM relative to cases with VTT only. Patients with both PFI and RSFI showed increased CSM compared with patients with either PFI or RSFI. ? Our results suggest TFI should be accurately evaluated and included in routine pathological reports to provide better patient risk stratification.     

囊性肾癌的诊治及预后(附31例报告)

目的提高囊性肾癌的诊治水平，提高对于囊性肾癌的认识。方法回顾性分析1994年6月-2004年6月收治的31例囊性肾癌患者的流行病学、病理学、临床表现、影像学特征及临床治疗资料，并与TNM分期构成与囊性肾癌组相同的21例非囊性肾癌比较预后。结果囊性肾癌无特征性的临床表现，术前影像学检查可以提供诊断线索，经病理确诊肾癌囊性变19例，多囊性肾癌9例，单纯性囊肿癌变3例。17例行根治性肾切除术，14例行单纯性肾切除术。术后21例获得随访，生存时间平均38个月。总体上与非囊性肾癌的预后尤统计学差异。站论囊性肾癌是一类在影像学和大体病理上具有囊性改变的肾癌的统称，由3种病理学类型构成，术前正确鉴别各亚型是选择手术方式和判断预后的关键。     

Long-term followup of patients with renal cell carcinoma treated with radio frequency ablation with curative intent

PURPOSE: We defined the role of radio frequency ablation in the treatment of renal cell carcinoma. MATERIALS AND METHODS: A total of 16 patients with biopsy proven renal cell carcinoma were treated with radio frequency ablation in an outpatient setting and followed for a minimum of 4 years. RESULTS: Of the 16 patients 5 died before 4 years of followup of unrelated causes. All except 1 tumor was successfully treated. All patients with exophytic tumors were successfully treated. CONCLUSIONS: Radio frequency ablation of exophytic renal cell carcinomas less than 5 cm in diameter is effective in eradicating the tumor and comparable to surgical extirpation at 4 years.     

Urinary collecting system invasion in renal cell carcinoma: Incidence and long-term prognosis

Objectives:   Current data on the prognostic impact of urinary collecting system (UCS) invasion by renal cell carcinoma (RCC) are highly conflicting. The aim of the present study was to assess incidence and long-term prognosis of RCC patients with and without UCS involvement.
Methods:   We evaluated 780 patients who had undergone renal surgery between 1990 and 2005. The mean follow-up was 5.44 years.
Results:   Sixty-seven patients (8.6%) demonstrated UCS invasion. These patients had a significant increase in the likelihood of cancer-related death (hazard ratio [HR] 1.9, 95% confidence interval: 1.4–2.7; P  = 0.001). Their median 5-year tumor-specific survival rate was 61%, as opposed to 79% for patients without UCS invasion ( P  = 0.001). UCS invasion was significantly associated with tumor stage, grade, clinical symptoms, lymph node and visceral metastasis at diagnosis, but not with age, gender, histologic subtype or body mass index. However, by means of multivariate analysis, UCS invasion was disqualified as an individual prognostic marker for RCC.
Conclusion:   We do not advocate the inclusion of UCS invasion into upcoming Tumor-Nodes-Metastasis staging systems. In contrast, future research should focus on the prognostic role of novel molecular tumor markers and/or specific immunological characteristics of RCC patients.     

Cachexia-like symptoms predict a worse prognosis in localized t1 renal cell carcinoma

PURPOSE: Although cachexia is a common sequela of advanced and metastatic renal cell carcinoma (RCC), cachexia-like symptoms may also represent a paraneoplastic finding. We assessed the prognostic significance of these symptoms in patients with stage T1 RCC. MATERIALS AND METHODS: Using the kidney cancer database at our institution 250 patients were identified who underwent partial or radical nephrectomy for T1N0M0 RCC between 1989 and 2001. The prognostic significance of the symptoms present at diagnosis and findings on preoperative laboratory evaluation were examined. RESULTS: Mean and median followup was 33 and 43 months, respectively. Malaise, weight loss, anorexia and hypoalbuminemia were cachexia related findings that were significant predictors of worse disease specific survival (DSS). DSS in patients with 1 vs greater than 1 cachexia related symptoms was not significantly different (p = 0.077). Therefore, any patient with at least 1 cachexia related finding was considered to be positive for cachexia and cachexia occurred in 37 (14.8%). Cachexia was associated with significantly worse recurrence-free survival (HR 3.03, p = 0.032) and DSS (HR 4.39, p = 0.011) even after controlling for tumor size, grade and performance status. The 5-year survival rate in patients with low grade (1 or 2) tumors with and without cachexia was 91% and 81%, respectively. The 5-year survival rate in patients with high grade (3 or 4) tumors with and without cachexia was 75% and 55%, respectively. CONCLUSIONS: Cachexia-like symptoms independently predict a worse prognosis in patients with T1 RCC. Patients with cachexia (malaise, weight loss, anorexia and hypoalbuminemia), especially when associated with high grade tumors, should be considered for clinical trials of adjuvant therapies.     

白藜芦醇对肾癌细胞体外增殖与侵袭能力的影响

目的探讨白藜芦醇对肾癌786-O与ACHN细胞体外迁增殖与侵袭能力的影响及可能的机制。方法 MTT检测白藜芦醇对肾癌细胞增殖能力的影响,划痕实验检测白藜芦醇对786-O与ACHN细胞体外迁移能力的影响,Transwell实验检测白藜芦醇对786-O与ACHN细胞体外侵袭能力的影响,RT-PCR与Western bolt检测白藜芦醇对MMP-2与MMP-9蛋白表达水平的影响。结果白藜芦醇可抑制膀胱癌细胞体外生长能力,且呈剂量依赖性。30μmol/L白藜芦醇处理786-O与ACHN细胞24h后,划痕实验发现白藜芦醇可抑制786-O与ACHN细胞体外迁移能力,Transwell实验证实白藜芦醇可抑制肾癌细胞786-O与ACHN的体外侵袭能力。RT-PCR与Western bolt结果表明,白藜芦醇可从mRNA与蛋白水平抑制MMP-2与MMP-9的表达。结论白藜芦醇能抑制肾癌细胞体外增殖能力,可能通过下调MMP-2与MMP-9的表达而抑制肾癌细胞786-O与ACHN体外迁移与侵袭能力,有望成为治疗肾癌的新策略。     

Living donor renal transplantation with incidental renal cell carcinoma from donor allograft

To report our series of cases with living donor kidney transplant by laparoscopic nephrectomy with incidental renal cell carcinomas (RCC) at the time of transplant. We performed a search of cases of renal allografts from living donors with incidental tumors which were confirmed as RCC in final pathology. The graft nephrectomy was performed via hand‐assisted laparoscopic procedure. All cases underwent partial nephrectomy of the tumor during the back‐table preparation of the graft and sent for pathological analysis. We performed 435 living donor kidney transplants at our Institution and identified four cases consistent with the diagnosis of RCC. Two of them were clear cell type, one papillary and one multilocular RCC. All the tumors presented at stage I of TNM classification. After a median follow‐up of 36 months, three patients remain free of dialysis with good allograft function. One noncompliant patient presented with a glomerular filtration rate (GFr) below 15 ml/min after a BK viral infection. At the end of follow‐up period, all patients had remained free of tumor. Donors with suspicious renal masses might be accepted for living donation. Partial nephrectomy before transplantation could offer a cure for the disease without risks for the recipient with therapeutic benefit for the donor.     

Sprouty2蛋白表达对肾癌细胞功能影响的实验研究

目的研究Sprouty2蛋白的表达水平对肾癌细胞增殖、侵袭等生物学功能的影响。方法采用RNAi技术,构建质粒转染肾癌细胞系786-O,建立Sprouty2低表达细胞株,通过MTT、Transwell等技术研究Sprouty2蛋白的表达水平对肾癌细胞增殖、侵袭等生物学行为的影响。结果成功构建Sprouty2低表达肾癌细胞系。当Sprouty2表达水平下调后,肾癌细胞的增殖、侵袭能力增强,与对照组及空质粒转染组比较差异有显著性（P〈0.05）。结论 Sprouty2的表达对肾癌细胞的功能有一定影响,Sprouty2表达越低,肾癌细胞的增殖及侵袭力越强。     

Metachronous bilateral renal cell carcinoma: risk assessment, prognosis and relevance of the primary-free interval

PURPOSE: We evaluated the prognosis, risk factors and relevance of the primary-free interval in a large cohort with metachronous bilateral renal cell carcinoma. MATERIALS AND METHODS: We studied 120 patients with metachronous, bilateral renal cell carcinoma who were treated at 12 international academic centers. Logistic regression was performed to evaluate risk factors for contralateral metachronous renal cell carcinoma during followup. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median age at diagnosis of the first and second renal cell carcinomas was 54 and 62 years, respectively. The most common histological subtype was bilateral clear cell renal cell carcinoma (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was found in 81%. The 15-year disease specific survival rates for the first and second renal cell carcinomas were 66% and 44%, respectively. Logistic regression revealed von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age as independent risk factors for contralateral renal cell carcinoma after surgery for unilateral renal cell carcinoma. A longer primary-free interval was associated with a better prognosis. When calculating disease specific survival from the diagnosis of the first renal cell carcinoma, the primary-free interval was an independent prognostic factor. CONCLUSIONS: Long-term survival rates of metachronous, bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age are independent risk factors for contralateral renal cell carcinoma. These risk factors support close and extended abdominal surveillance following nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary-free interval have a more favorable prognosis.