Factor In Renal Cell Carcinoma Research Articles

Prognostic effect of serum C-reactive protein kinetics on advanced renal cell carcinoma treated with sunitinib.

C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the prognostic effect of pretreatment serum CRP level and CRP kinetics on patients with advanced RCC treated with sunitinib. A total of 56 consecutive patients with advanced RCC treated with sunitinib between December, 2008 and December, 2012 were enrolled in the present study. The patients were retrospectively divided into 3 cohorts according to pretreatment serum CRP level and CRP kinetics: i) Normal CRP cohort (pretreatment CRP ≤0.30 mg/dl); ii) normalized CRP cohort (pretreatment CRP >0.30 mg/dl that normalized within 2 cycles of treatment); and iii) non-normalized CRP cohort (pretreatment CRP >0.30 mg/dl that did not normalize after sunitinib initiation). Disease control rate, progression-free survival and overall survival times were compared for the 3 cohorts. The normal (n=17, 30.4%) and the normalized (n=8, 14.3%) CRP cohorts exhibited significantly better disease control rates compared with the non-normalized CRP cohort (n=31, 55.4%; P<0.0001 and P=0.0445, respectively). The normal CRP cohort exhibited significantly longer progression-free survival compared with the non-normalized CRP cohort (P=0.0050). The normal and normalized CRP cohorts exhibited significantly longer overall survival compared with the non-normalized CRP cohort (P=0.0005 and 0.0466, respectively). Therefore, CRP kinetics and normal pretreatment CRP level are prognostic indicators in patients with advanced RCC treated with sunitinib.

IJU this issue

Have you ever noticed morphological variations in inferior vena cava thrombus associated with renal cell carcinoma (RCC)? Do you feel any difficulty in determining the T factor of RCC (T3a or T3b) because the invasion of the inferior vena cava wall by the cancer cannot be precisely evaluated in the preoperative computed tomography or magnetic resonance imaging (MRI)? Choi et al. (Seoul, Korea) have shown challenging data connecting morphological features and the prognosis of non-metastatic RCC with inferior vena cava thrombus. They classified two types, namely, spherical (type 1) and speculated (type 2). A total of 29 patients had type 1 (18.6%), and 127 patients had type 2 (81.4%). Type 1 had a better prognosis than type 2 in overall survival and cancer-specific survival. Here arises a fundamental question. What is the biological background that makes these differences? Conceivably, well-marginated, firm cancer with abundant connective tissues makes type 1, whereas friable and disintegrating cancer makes type 2. However, abundant connective tissue is occasionally observed in sarcomatoid RCC showing a poor prognosis.1 If consistency can be evaluated by imaging, that helps precise preoperative staging. Clinical implications are that this helps the indication of an umbrella stent that blocks pulmonary embolism. A preoperative umbrella stent should be considered in type 2, because friable cancer tissue is likely to break off. Concordantly, in this cohort, perioperative mortality was higher in type 2. Do you think that aged patients with testicular germ cell tumors have a poor prognosis in comparison with young patients? Our feelings are “yes,” because aged patients cannot tolerate the standard chemotherapeutic regimen because of morbidities. Kawai et al. (Tokyo, Japan) described a Japanese cohort of patients aged 50 years and older. Of the 1119 cases, 123 (11.0%) were diagnosed at age ≥50 years. They were frequently seminomas, and more frequently diagnosed in clinical stage 1 than younger patients. Regarding metastatic cases, aged patients are classified more as the better prognosis group; however, cancer-specific survival was not superior to younger patients. This is due to the fact that not enough chemotherapy was given to the aged patients. They suggested alternative regimens without bleomicin for aged patients with comorbidities. Adenocarcinoma (ADK) of the bladder is rare. We vaguely believe that ADK has a poorer prognosis than urothelial carcinoma of the bladder. Is it really so? Using the SEER database of 10 024 patients with non-metastatic bladder cancer, Zaffuto et al. (Milan, Italy) have shown that 215 (2.1%) had ADK. Interestingly, cancer-specific mortality rates did not defer from urothelial carcinoma. A higher cancer-specific mortality applies to the signet ring cell variant. Among ADK patients, 30.7% harbored the signet ring cell variant. The signet ring cell variant should be paid attention to when ADK is pathologically diagnosed. Classical 12-core transrectal ultrasound-guided biopsy is limited to detecting clinically significant prostate cancer. Multiparametric MRI (mpMRI) has been widely used to facilitate the accurate diagnosis of clinically significant cancer. Tsivian et al. (Durham, USA) analyzed the accuracy of mpMRI in a repeat biopsy cohort of 50 cases using comprehensive transperitoneal mapping biopsy as the reference. mpMRI had high specificity and a high negative predictive value for detecting clinically significant prostate cancer. However, in our daily practice, target biopsy is the standard procedure, which might miss a relevant number of clinically significant prostate cancers, as mentioned by Kesch et al. (Heidelberg, Germany). We published a paper evaluating the prognostic marker of mpMRI for predicting biological recurrence after radical prostatectomy.2 We took Prostate Imaging Reporting and Data System 4/5 as positive, and showed that mpMRI was an independent biomarker for biological recurrence. We believe mpMRI is an effective index for determining the therapeutic strategy, as well as a the follow-up strategy.

Obesity, Diabetes Mellitus, Hypertension and other Risk Factors for Renal Cell Carcinoma in Japan: A Mini-Review

Background: The incidence of kidney cancer is high in Western Europe, Northern Europe and North America, while it is low in Asia. Although the incidence of kidney cancer in Japan is lower than the rates in the other industrialized countries, there is no doubt that it is increasing. In this paper, we would like to introduce the result of epidemiological studies, which evaluate the non-genetic risk factors for kidney cancer in the Japanese population. Methods: Relevant studies were identified in the PubMed database using the combination of “Japan”, “kidney cancer”, “renal cell cancer” and “risk”, and the ICHUSHI database (Japanese database) using a combination of “kidney cancer /renal cell cancer”, and “risk factor”. In addition, we selected one cohort study from the references of these reports. Results and Discussion: Several studies were identified in the database. In these studies, obesity, diabetes mellitus, hypertension, kidney diseases, chronic renal disease with dialysis, tobacco smoke, fondness for fatty food, milk, and black tea are associated with an increased risk of kidney cancer. On the other hand, an inverse association with the kidney cancer risk is found for an intake of starchy roots (i.e., taro, sweet potato and potato), physical activity and educational level. In Japan, however, drinking black tea and milk may be surrogates for a westernized dietary habit while eating starchy roots may be a surrogate for a traditional Japanese dietary habit. Additional studies are needed to confirm the risk factors for kidney cancer in the Japanese population.

Preoperative Albumin to Globulin Ratio (AGR) as Prognostic Factor in Renal Cell Carcinoma.

Background: Malnutrition and systemic inflammatory response are frequently associated with prognosis in patients with several types of cancer, including renal cell carcinoma (RCC). The study is aimed to investigate the ability of preoperative serum albumin to globulin ratio (AGR) to predict the long-term mortality of RCC patients.Methods: The study is a retrospective study of an unselected cohort of 895 RCC patients who underwent a curative radical or partial nephrectomy at the Department of Urology in the Sun Yat-Sen University Cancer Center between January 2000 and December 2012 and had documented preoperative serum total protein and albumin (ALB) levels. The preoperative AGR was calculated as the ratio of ALB to (total protein-ALB) and its association with other clinical indices was assessed using survival analysis.Results: Low preoperative AGR was associated with older population, lower hemoglobin, higher total protein, lower ALB, lower body mass index and advanced stage. The univariate and multivariate Cox analyses demonstrated that preoperative AGR was an independent prognostic indicator of overall survival (OS) (hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.43 to 0.93, P=0.022). In addition, patients with low preoperative AGR at pT1-2, pT3-4, pN0, pN1, pM0 and pM1 stages had significantly shorter OS than patients with high preoperative AGR.Conclusion: Preoperative AGR is a proven objective, reproducible, inexpensive survival predictor of RCC patients following surgical resection and should be considered for routine clinical use.

Overall prognostic impact of C-reactive protein level in patients with metastatic renal cell carcinoma treated with sorafenib.

C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the overall prognostic impact of CRP in patients with metastatic RCC treated with sorafenib. Between April 2008 and December 2014, 40 consecutive patients with metastatic RCC were treated with sorafenib at our institution. The patients were divided into two cohorts according to the pretreatment CRP level: (i) a normal CRP cohort (≤0.30 mg/dl) and (ii) an elevated CRP cohort (>0.30 mg/dl). Kaplan-Meier overall survival analysis was carried out. The effects of selected variables on survival were assessed by multivariate regression using the Cox proportional hazards model. The normal CRP cohort included 16 patients (40.0%) and the elevated CRP cohort included 24 patients (60.0%). The normal CRP cohort showed significantly longer overall survival than the elevated CRP cohort (median, 52.0 vs. 17.0 months; P=0.0072). On multivariate analysis, normal CRP predicted longer overall survival (hazard ratio, 0.367; 95% confidence interval, 0.147-0.914; P=0.0313). Pretreatment normal CRP predicted better overall survival in patients with metastatic RCC treated with sorafenib and CRP level may be a useful biomarker for predicting overall survival of patients treated with sorafenib.

The Presence and Thickness of Pseudocapsule after Partial Nephrectomy in Renal Cell Carcinoma

Ya z›fl ma Ad re si/Ad dress for Cor res pon den ce: Dr. Fehmi Narter, Kartal Dr. Lutfi Kirdar Egitim ve Arastirma Hastanesi, Uroloji Klinigi, Istanbul, Turkiye E-mail: fehminarter66@gmail.com Ge lis Ta ri hi/Re cei ved: 20.06.2016 Ka bul Ta ri hi/Ac cep ted: 05.09.2016 © Uroonkoloji Bulteni, Ga le nos Ya yi ne vi ta ra fin dan ba sil mis tir. Bu makale “Creative Commons Alinti-Gayriticari-Turetilemez 4.0 Uluslararasi Lisansi (CC BY-NC 4.0)” ile lisanslanmistir. Objective: In this study, we aimed to evaluate the presence and thickness of pseudocapsule after partial nephrectomy in renal cell carcinoma (RCC) cases. Materials and Methods: A total of 100 patients who were admitted to our clinic and diagnosed with RCC were included in the study. Histopathological specimens of the patients who underwent partial nephrectomy were re-evaluated retrospectively. Results: The histopathological results revealed pseudocapsule in 87 cases (87%, median thickness: 0.708 mm). Pseudocapsule median thickness was noted respectively 0.483, 0.691, 0.737, 0.954 mm in Fuhrman Grade 0, 1, 2, 3/4 groups (p<0.05). Conclusion: In this study, a statistical significance was found between nuclear grading system and the thickness of pseudocapsule in RCC. We believe that it may be a prognostic factor for RCC in the future.

Abstract B18: CXCL10 suppresses tumor angiogenesis and impedes expression of critical angiogenic factors in renal cell carcinoma

Abstract Background: Angiogenic progress is complex and several factors are involved as a promoter or inhibitor of angiogenesis. Tumor can use the imbalance of pro- and antiangiogenic factors in progression. The CXC chemokine family are consisted of pro- or antiangiogenic factors. Recent studies revealed CXCL10 as an anti-angiogenic factor in response to angiogenic factors like bFGF or VEGF. However, a role of CXCL10 in cancer and angiogenesis is unclear. Here, we investigated the role of CXCL10 on tumor angiogenesis and its mechanisms in renal cell carcinoma. Methods: Human vascular endothelial cell (HUVEC) was used to evaluate the effects of CXCL10 on endothelial cells. MTS assay was performed to assess cell proliferation. Cell cycle analysis was performed using flow cytometry with propidium iodide. RT-PCR and western blot were performed to assess the baseline expression of CXCL10 in a panel of renal cell carcinoma cells. Overexpression of CXCL10 was developed by lentiviral transfection. Quantitative RT-PCR for angiogenic factors (VEGF, PDGF, FGF, MMP9) was performed by angiogenesis multigene screening array. Subcutaneous tumor xenografts were developed using Caki-1 cells to evaluate in vivo effects of CXCL10. Results: CXCL10 inhibited proliferation and tube formation of HUVEC in a dose-dependent manner, while it did not affect in vitro tumor proliferation of renal cell carcinoma cells. Expression of CXCL10 was downregulated in Caki-1, UMRC3 and UMRC6 cells. Overexpression of CXCL10 suppressed expression of angiogenic factors including VEGF-A, PDGF, FGF2 and MMP9 in Caki-1 cells, suggesting that CXCL10 is involved non only as an anti-angiogenic factor but also as a suppressor of critical angiogenic factors in renal cell carcinoma. In vivo Restoration of CXCL10 expression suppresses tumor growth in renal cell carcinoma by suppressing tumor angiogenesis in xenografts. Conclusions: CXCL10 has a role as an anti-angiogenic factor and also as a suppressor of critical angiogenic factors in renal cell carcinoma. Restoration of CXCL10 expression suppresses tumor growth in renal cell carcinoma by impeding expression of other angiogenic factors including VEGF, PDGF, FGF, MMP9 in renal cell carcinoma as well as inducing anti-angiogenic effect on endothelial cells. Our data suggest that targeting CXCL10 might be a novel therapeutic option for advanced renal cell carcinoma. Citation Format: Hyun A Jin, Jun Hyeok Heo, You Hyun Kang, Ki Hong Kim, Kyung Suk Han, Sung Joon Hong. CXCL10 suppresses tumor angiogenesis and impedes expression of critical angiogenic factors in renal cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B18.

Abstract 2634: Prognostic value of obesity-related genes methylation in localized renal cell carcinoma patients

Abstract Obesity is an established risk factor for renal cell carcinoma (RCC): more than 40% of RCC cases in US are attributed to excessive body weight. Growing evidence suggests that obesity may also be associated with the prognosis of RCC. The molecular mechanism linking obesity and RCC is not well understood. In the present study, we evaluated the association between promoter CpG island methylation of 20 obesity-related genes and RCC. A total of 275 newly diagnosed and previously untreated Caucasian RCC patients were included. For the discovery population, 75 tissue pairs of RCC tumors and normal adjacent tissues from the surrounding kidney were used and for the validation population an additional 200 pairs were included. Pyrosequencing was used to determine CpG site methylation on bisulfite-treated genomic DNA. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confident intervals (CIs) for the association of CpG methylation with recurrence and Kaplan-Meier curve to plot disease free survival (DFS) time by different CpG site methylation. The average age of the patients was 59 years and they were largely males; ∼50% were never smokers. Most of the cases were clear cell RCC (ccRCC) and clinical stage I. Among the 20 markers, LEP, LEPR and NPY were significantly hypermethylated in tumor tissues compared to normal tissues (p&amp;lt;0.0001) in the discovery set. Similar results were obtained in the validation set. Moreover, LEPR methylation in tumors was associated with recurrence. When patients were dichotomized into high and low methylation groups according to the median value of LEPR methylation, high LEPR methylation was associated with a significantly higher risk of recurrence (HR = 2.4, 95% CI, 1.03-5.8), adjusted by age, gender, clinical stage, grade, smoking status, BMI, hypertension and histology. The Kaplan-Meier analysis showed a shorter 5-year DFS probability for the patients with high LEPR methylation level (34.7%) compared with low methylation (41.7%) (LogRank, p = 0.032). The MST was 39 months in high methylation group and 47 months in low methylation. Our results suggest that LEPR hypermethylation in tumors is associated with recurrence in RCC patients and thus LEPR may provide a functional link between obesity and RCC. Future studies are needed to elucidate the biology underlying the association of LEPR methylation and RCC recurrence. This work was supported in part by the National Institutes of Health (grant R01 CA170298) and the Center for Translational and Public Health Genomics, Duncan Family Institute for Cancer Prevention, The University of Texas MD Anderson Cancer Center. Citation Format: Julia Mendoza-Perez, Jian Gu, Nizar M. Tannir, Surena Matin, Jose A. Karam, Maosheng Huang, Shu Xiang, David W. Chang, Christopher G. Wood, Luis A. Herrera, Xifeng Wu. Prognostic value of obesity-related genes methylation in localized renal cell carcinoma patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2634.

Research advances and forecast of renal cell carcinoma

Renal cell carcinoma (RCC) is a common urological malignant carcinoma, also the most popular subtype of renal tumors. In the early stage of RCC, patients always have less clinical symptoms, which leads to the poor prognosis. Renal carcinogenesis is involved in the cytogenetic and molecular alterations. What's more, the understanding of RCC was improved since the development and the application of the molecular biology and genomics experimental technique, including the pathogenesis and etiology, targeted therapeutic strategies and prognostic factors of RCC. The goal of this review is to overview the research advances of renal tumors. Key words: Renal cell carcinoma; Therapeutic strategy

Expression and correlation of HLA-G and sHLA-G as prognostic factors in renal cell carcinoma.

e16066Background: many studies have related HLA-G to increased tumorigenicity. Serum HLA-G (sHLA-G) has been detected in plasma of patients with malignant diseases. Levels of sHLA-G are higher in p...

AB009. Prognostic outcomes and risk factors for patients with renal cell carcinoma and venous tumor thrombus after radical nephrectomy and thrombectomy: the prognostic significance of venous tumor thrombus level

BackgroundTo evaluate the prognostic outcomes and risk factors for renal cell carcinoma (RCC) patients with venous tumor thrombus in China.MethodsWe reviewed the clinical information of 256 patients who underwent radical nephrectomy and thrombectomy. Overall and cancer-specific survival rates were analyzed. Univariate and multivariate analyses were used to investigate the potential prognostic factors.ResultsThe median survival time was 45 months. The 5-year overall survival and cancer-specific survival rate were 44.2% and 47.2% for all patients. No matter for all patients or N0M0 patients, significant survival difference were observed between four different tumor thrombus levels, and between early (below hepatic vein) and advanced (above hepatic vein) tumor thrombus. Multivariate analysis demonstrated that higher tumor thrombus level (P=0.016, RR =1.58), N (P=0.013, RR =2.60), M (P<0.001, RR =4.14) stages and adrenal gland invasion (P=0.001, RR =4.91) were the most significant negative prognostic predictors.ConclusionsIn this study, we reported the most cases of RCC patients with venous extension in China. We proved that patients with RCC and venous tumor thrombus may have relative promising long-term survival rate, especially for those with early tumor thrombus.

Occupation as a risk factor for renal cell cancer: a nationwide, prospective epidemiological study

Objective Using centralized registries in Iceland, the aim of this study was to prospectively investigate multiple risk factors for renal cell carcinoma (RCC), including occupational history. Materials and methods From the Reykjavik study database, 18,840 men and women born in the period 1907–1935 were linked with a population-based registry containing all RCCs diagnosed in Iceland from 1971 to 2005 (n = 910). From this cross-reference, altogether 225 cases were identified. A prospective analysis of the risk factors for RCC was performed using Cox regression analysis, from the time of entry into the Reykjavik study to the diagnosis of RCC, death or end of follow-up, with a median follow-up time of 25 years. The hazard ratio (HR) was then calculated for multiple risk factors including occupational history. Results Male gender [HR 1.65, 95% confidence interval (CI) 1.14–2.38], body mass index (BMI) over 25 kg/m² (HR 1.41, 95% CI 1.06–1.88) and age (HR 1.04, 95% CI 1.03–1.07) increased the risk of RCC, as did severe hypertension (>160/100 mmHg) (HR 1.46, 95% CI 1.05–2.03) and history of kidney disease (HR 1.55, 95% CI 1.11–2.16); however, smoking and type 2 diabetes were not significantly associated with the disease. The risk of RCC was significantly increased in painters (HR 2.97, 95% CI 1.31–6.74), aircraft mechanics (HR 4.51, 95% CI 1.11–18.28) and shipbuilders (HR 2.03, 95% CI 1.06–3.84). Conclusions Together with male gender, advanced age, hypertension, BMI over 25 kg/m² and history of kidney disease, the risk of RCC was significantly increased in painters, aircraft mechanics and shipbuilders, suggesting a link to occupational exposure.

Effect of hypertension on preoperative neutrophil-lymphocyte ratio evaluation of prognosis of renal cell carcinoma

ObjectivesAs an indicator of inflammatory reaction of immune system, the neutrophil-lymphocyte ratio (NLR) is a significantly independent prognostic factor of renal cell carcinoma (RCC). However, the NLR was not added in any well-established prognostic models. Many physiologic factors were also associated with NLR, such as hypertension. As such, we evaluated the effect of hypertension on NLR evaluation of prognosis of RCC. Materials and methodsHematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 401 patients with RCC between the years 1999 and 2009. The standardized cutoff-finder algorithm was used to find the suitable NLR cutoff value for recurrence. The Log-rank test and Kaplan-Meier method were used to compare and estimate the recurrence-free survival. Univariate and multivariate Cox regression analyses were used to evaluate the association between NLR and clinicopathologic outcomes. ResultsIn the analysis of total subjects, recurrence-free survival was significantly worse among patients with a preoperative NLR (>3.139 [21.9%] vs.≤3.139 [78.1%]; P<0.001). High NLR value was associated with high pathological TNM stage (P = 0.009, 0.018, 0.001, respectively). In the normotensive subgroup, recurrence-free survival was also significantly worse among patients with a preoperative NLR (>3.139 [22.6%] vs.≤3.139 [77.4%]; P<0.001). However, in the subgroup with hypertension, the difference of recurrence-free survival was not significant between patients with preoperative NLR (>3.139 [21.2%] vs.≤3.139 [78.8%]; P = 0.093). Moreover, multivariate analysis identified increased NLR as a poor prognosis index for recurrence-free survival in total group (hazard ratio [HR] = 2.27; 95% CI: 1.50–3.44; P<0.001) and normotensive subgroup (HR = 2.97; 95% CI: 1.74–5.07; P<0.001), but not in hypertensive subgroup (HR = 1.25; 95% CI: 0.59–2.65; P = 0.566). ConclusionsHypertension is a disturbance factor in the evaluation of prognosis of RCC by preoperative NLR.

Association between diabetes mellitus and the survival of sunitinib-treated patients with metastatic renal cell carcinoma.

546 Background: Diabetes mellitus is one of the major risk factor for renal cell carcinoma (RCC) development. Although, in various cancers, the relationship between diabetes mellitus and worse prognosis is pointed out, the association between RCC prognosis and diabetes mellitus is under discussion. We sought to determine the association between diabetes mellitus with outcome of sunitinib treatment in metastatic RCC (mRCC) patients. Methods: A retrospective study of sunitinib-treated mRCC patients was performed. 69 patients who had been treated with sunitinib in Japanese two institutions (Teikyo University Chiba Medical Center and Chiba University) were entered. Kaplan-Meier and the log-rank test were performed to investigate the association between the pretreatment status of diabetes mellitus and the outcome of the patients who received the treatment with sunitinib. Results: Between 2008 and 2015, 69 mRCC patients were treated with sunitinib. 53 (76.8%) patients received sunitinib treatment as the first line molecular target drug. 15 (21.7%) patients were diagnosed as diabetes mellitus at the time of sunitinib treatment. Median time to treatment failure (TTF) was 7.1 months, cancer specific survival (CSS) was 33.9 months for all patients. With regard to TTF, there was no difference between diabetic and non-diabetic patients, 9 months for diabetic patients and 7.1 months for non-diabetic patients respectively (P = 0.3271). CCS was significantly shorter for diabetic patients, 11 months for diabetic patients and 39.4 months for non-diabetic patients respectively (P = 0.0469). When focusing on HbA1c, CSS was significant longer for the patients with HbA1c under 6.5% than the patients with HbA1c was 6.5 or more, median CSS was 44.5 months and 11.3 months, respectively (P = 0.0055). Conclusions: Diabetes mellitus did not influence the TTF of sunitinib treatment for mRCC patients. Diabetes mellitus may negatively affect the CSS of sunitinib-treated mRCC. Clinicians should consider controlling patient’s HbA1c status at the initiation of sunitinib treatment for mRCC.

Treatment, Outcome and Prognostic Factors in Renal Cell Carcinoma - A Single Center Study (2000-2010).

In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitors (TKI) and mTOR inhibitors (mTORi), have a largely better outcome than those who have less exposure to these agents. The value of the prognostic scores developed by Motzer and Heng is fully reflected by the outcomes according to prognostic risk groups in our unselected patient cohort. Also, the use of surgical intervention appears to be an important prognostic factor, however with a somehow diminished effect by novel systemic therapies. The importance of multiple lines of targeted therapies is underlined by this retrospective analysis. For patients with metastatic RCC not receiving targeted therapy the median OS was 22.6 months compared to those with one TKI 25.4 months. Patients receiving a second-line therapy (median overall survival 27.6 months) and those patients with three or more lines of therapy (43.8 months) have the greatest benefit. Also, exposure to a mTORi improves survival versus non-exposure to mTORi (63.3 vs. 22.3 months, p=0.038). In conclusion a trend towards improved survival is confirmed for an unselected population when the full variety of therapeutic options is available and can be used for the individual patient.

A clinical study of patients with renal cell carcinoma

Background: In 1894 Lubarch endorsed the idea of these being a suprarenal original tumour, and the term “hypernephroid tumors” indicating origin above the kidney was advocated by Birch-Hirschfeld. It was this semantic and conceptual mistake that led to the introduction of the term “hypernephroma”, which predominates in the literature describing parenchymal tumours of the primary renal origin. The objective was to study the surgical profile, treatment modalities for patients with renal cell carcinoma. Methods: Present study was retrospective as well as prospective study and was carried out in the Department of Surgery, Government Medical College and Hospital; Auragnabad for a period of one year Retrospective study was done from the record in Radiotherapy Department of this college. Prospective study was done with the number of cases of kidney tumors admitted during the study period. Total number of cases studied were 44, out of these, 26 was studied retrospectively and 18 cases prospectively. Patients who were absconded after admission are also included. Results: The youngest patient of renal cell carcinoma was found to be of 35 years, and oldest of 70 years old. The maximum incidence was found in 5th and 6th decade of life. In this treatise, maximum numbers of cases were presented with lump in abdomen (78.27%), and classic triad of pain, lump and hematuria was only in 4 cases (17.40%). Maximum numbers of patients were in stage III and IV. Anemia was found only in 6 cases (26.10%) and raised E.S.R. in 2 cases (08.70%). Not a single patient showed hypercalcemia or erythrocytosis. Most commony used treatment modality in our patients was Nephrectomy + RT + CT + HT in 9 cases (39.13%). Conclusions: Commonest etiological factor for renal cell carcinoma is smoking (30.50% of the cases). Maximum cases of renal cell carcinoma were presented with lump in abdomen and classic triad was found in only 17.4% of cases (i.e. pain, hematuria and lump). Maximum cases of renal cell carcinoma were found to be in stage III and IV. Majority of the renal cell carcinomas were treated with nephrectomy, postoperative radiotherapy, chemotherapy and hormonal therapy in combination.

Biomolecular prognostic factors in renal cell carcinoma: a literature review

While analyzing data from domestic and foreign literature, we looked at various molecular factors of kidney tumors, some of which may be considered as diagnostic and prognostic markers of the clinical course of the cancer process. Here presented also is an assessment of the possible use of these indicators, in conjunction with other classic factors, in the prognosis of survival and the evaluation of the risk of metastasis in renal cancer.

The role of glutathione transferases in renal cell carcinoma

Mounting evidence suggest that members of the subfamily of cytosolic glutathione S-transferases (GSTs) possess roles far beyond the classical glutathione-dependent enzymatic conjugation of electrophilic metabolites and xenobiotics. Namely, monomeric forms of certain GSTs are capable of forming protein: protein interactions with protein kinases and regulate cell apoptotic pathways. Due to this dual functionality of cytosolic GSTs, they might be implicated in both the development and the progression of renal cell carcinoma (RCC). Prominent genetic heterogeneity, resulting from the gene deletions, as well as from SNPs in the coding and non-coding regions of GST genes, might affect GST isoenzyme profiles in renal parenchyma and therefore serve as a valuable indicator for predicting the risk of cancer development. Namely, GSTs are involved in the biotransformation of several compounds recognized as risk factors for RCC. The most potent carcinogen of polycyclic aromatic hydrocarbon diol epoxides, present in cigarette smoke, is of benzo(a)pyrene (BPDE), detoxified by GSTs. So far, the relationship between GST genotype and BPDE-DNA adduct formation, in determining the risk for RCC, has not been evaluated in patients with RCC. Although the association between certain individual and combined GST genotypes and RCC risk has been debated in a the literature, the data on the prognostic value of GST polymorphism in patients with RCC are scarce, probably due to the fact that the molecular mechanism supporting the role of GSTs in RCC progression has not been clarified as yet.

Association of neutrophil-to-lymphocyte ratio with the prognosis in patients with renal cell carcinoma

Objective To explore prognostic factors of renal cell carcinoma and investigate the association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of renal cell carcinoma (RCC) in patients who received nephrectomy treatment. Methods We retrospectively reviewed the records of 1325 patients with renal cell carcinoma who underwent nephrectomy between January, 2008 and December, 2012. We retrospectively analyzed the clinicopathologic characteristics of patients. The optimal cutoff value for NLR was determined using receiver operating characteristic curve (ROC) analysis. We defined them as high NLR group when NLR ≥ 2.7 and low NLR group when NLR<2.7. Overall survival (OS) and recurrence free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate models were used to analyze the association of NLR with clinicopathologic outcomes. Results By the end of the study, 1220 cases were followed up. The follow-up rate was 92.1%. Mean follow-up was 40 months (range 2 months to 87 months). The three-year and five-year overall survival rate were 91.3% and 86.9%, respectively. Meanwhile the three-year and five-year recurrence free survival rate were 88.2% and 85.8%, respectively. 2.7 was selected as the optimal cutoff value to differentiate between low NLR and high NLR. A NLR ≥2.7 was significantly associated with worse 5-year overall survival and worse 5-year recurrence free survival than a NLR 65, presentation mode with symptom, higher tumor stage, higher Fuhrman grade, histologic subtype, neutrophil count≥4.5, lymphocyte count<1.7, NLR ≥2.7 significantly correlated with poor OS on univariate analysis. Multivariate analysis revealed that higher tumor stage, preoperative NLR ≥2.7 at diagnosis were poor independent prognostic factors for OS of renal cell carcinoma. Conclusion High NLR was independent poor predictor of renal cell carcinoma. Key words: Carcinoma, renal cell; Neutrophil-to-lymphocyte ratio; Prognosis; Survival rate

Cellular Adaptation to VEGF-Targeted Antiangiogenic Therapy Induces Evasive Resistance by Overproduction of Alternative Endothelial Cell Growth Factors in Renal Cell Carcinoma

Vascular endothelial growth factor (VEGF)–targeted antiangiogenic therapy significantly inhibits the growth of clear cell renal cell carcinoma (RCC). Eventually, therapy resistance develops in even the most responsive cases, but the mechanisms of resistance remain unclear. Herein, we developed two tumor models derived from an RCC cell line by conditioning the parental cells to two different stresses caused by VEGF-targeted therapy (sunitinib exposure and hypoxia) to investigate the mechanism of resistance to such therapy in RCC. Sunitinib-conditioned Caki-1 cells in vitro did not show resistance to sunitinib compared with parental cells, but when tested in vivo, these cells appeared to be highly resistant to sunitinib treatment. Hypoxia-conditioned Caki-1 cells are more resistant to hypoxia and have increased vascularity due to the upregulation of VEGF production; however, they did not develop sunitinib resistance either in vitro or in vivo. Human endothelial cells were more proliferative and showed increased tube formation in conditioned media from sunitinib-conditioned Caki-1 cells compared with parental cells. Gene expression profiling using RNA microarrays revealed that several genes related to tissue development and remodeling, including the development and migration of endothelial cells, were upregulated in sunitinib-conditioned Caki-1 cells compared with parental and hypoxia-conditioned cells. These findings suggest that evasive resistance to VEGF-targeted therapy is acquired by activation of VEGF-independent angiogenesis pathways induced through interactions with VEGF-targeted drugs, but not by hypoxia. These results emphasize that increased inhibition of tumor angiogenesis is required to delay the development of resistance to antiangiogenic therapy and maintain the therapeutic response in RCC.