Incidence Of Renal Cell Cancer Research Articles

Analysis of risk factors affecting the postoperative drainage after a laparoscopic partial nephrectomy: a retrospective study.

Laparoscopic partial nephrectomy (LPN) remains the most commonly used measure for treating localized renal cell cancer (RCC) with an increasing incidence of RCC ever since the 1990s. This study aimed to identify risk factors that affect the postoperative time of drainage and total drainage volume after LPN. The clinical data of 612 RCC patients who received LPN from January 2012 to December 2022 in our hospital, including the postoperative drainage time and total drainage volume, were retrospectively analyzed. Univariable and multivariable linear regression and correlation analyses were used to identify the correlations between 21 factors, which include gender, age, history of alcohol consumption, family history of RCC, body weight, body mass index (BMI), and operation time, postoperative drainage time, and total drainage volume. The mean time of drainage was 3.52 ± 0.71 days (range: 2 to 8 days), with an average total drainage volume of 259.83 ± 72.64 mL (range: 50 to 620 mL). Both univariable and multivariable linear regression analyses revealed several statistically significant associations. Gender (p = 0.04), age (p = 0.008), smoking history (p < 0.001), diabetes (p = 0.032), operation time (p = 0.014), and BMI (p = 0.023) were identified as significant factors associated with the time of drainage. On the other hand, age (p = 0.008), smoking history (p < 0.001), diabetes (p = 0.006), and BMI (p = 0.016) emerged as independent risk factors influencing the total drainage volume. The duration of postoperative drainage was found to be associated with gender, age, smoking history, diabetes, operation time, and BMI. In contrast, the total drainage volume was primarily influenced by age, smoking history, diabetes, and high BMI following LPN. For patients with these conditions, meticulous attention to hemostasis and bleeding control is crucial during the perioperative period.

Characteristics of the Patients Aged Less than 40 Years Operated for a Renal Mass.

The incidence of renal cell cancer (RCC) is low in individuals aged less than 40 years; however several studies have shown this increasing trend over the years. Hereditary syndromes are associated with RCC and are more frequently observed in early-onset cases. In this study, we investigated the characteristics of the patients, aged less than 40 years, who were operated for a renal mass with the suspicion of RCC. We analyzed patients aged <40 years who underwent partial or radical nephrectomy between January 2012 and December 2022. A total of 618 patients underwent partial or radical nephrectomy and 60 (9.7%) patients were aged <40 years. A total of 62 renal masses were resected. The median age of the patients was 34 (31.75-38) years. RCC was detected in 50 (80.6%) lesions, while 12 (19.4%) lesions were benign. The most commonly observed benign tumors were oncocytoma and multicystic nephroma. Low-stage RCC (stage 1) was detected in 78% of patients. Recurrence was observed in two patients and both had von Hippel-Landau gene mutation. During follow-up, two patients were found to have lung metastasis, while another patient had bone metastasis. Three patients died during the follow-up period. Disease free survival rate was 89.58% and cancer specific survival rate was 93.88%. The incidences of kidney cancer in young adults are increasing; therefore, early discovery and the diagnosis are important. Further research is required to gain a better understanding.

Advantages of multi-target scintigraphy in the diagnosis of kidney cancer

Background. There has been a recent increase in the incidence of kidney cancer, which is explained not only by the improvement in the diagnosis of neoplasms but also by a true increase in the incidence of renal cell cancer. This led to the need for in-depth study and solution of the following problem: to prove the benefits of multi-target scintigraphy for the assessment of the functional capacity of kidneys in establishing the diagnosis of kidney cancer and early detection of secondary lesion of the skeleton during the primary full examination of the patient, as well as in monitoring of the disease.&#x0D; Purpose. For the first time to prove diagnostic significance of a multi-target scintigraphic examination with a radiopharmaceutical drug with renal and osteotropic kinetics, in the form of a sequential combination of dynamic renal scintigraphy and osteoscintigraphy (as one diagnostic examination) in the early detection of secondary lesion of the bones of the skeleton and simultaneous determination of the functional capacity of kidneys in the pre-treatment period and in monitoring of the course of kidney cancer.&#x0D; Materials and methods. Dynamic renal scintigraphy and subsequent (within the next 3 hours) osteoscintigraphy with 99mTc-methylenediphosphonic acid (99mТс-MDP) (activity of 370–740 MBq) were performed on the SPECT-1 gamma camera «AMCRIS-H Limited» (Ukrainian-American enterprise) with computer software «Spect Work» (Ukraine) at the premises of the Department of Radiology and Radiation Medicine of Bogomolets National Medical University in the Department of Radionuclide Diagnostics of communal non-commercial enterprise&#x0D; «Kyiv City Clinical Hospital No.18». 20 patients with a morphologically established diagnosis of kidney cancer, aged from 38 to 68 years, were examined before the full diagnosis was established according to TNMx. As a control group, 8 patients with ultrasonography-confirmed cystic lesions of the kidneys were examined.&#x0D; Results. Using a radiopharmaceutical drug with renal and osteotropic kinetics in the form of a simultaneous sequential combination of dynamic renal scintigraphy and osteoscintigraphy (as one diagnostic examination) allowed us to assess the degree of deterioration of the filtering and excretory capacity of the kidneys regardless of the origin of the expansive process. The results of dynamic renal scintigraphy with 99mТс-MDP made it possible to assess functional capacity of the kidneys no worse than specific renal imaging agents in subsequently given possibility to determine secondary lesion of the bones of the skeleton in osteoscintigraphy. We established indicators of development of renal compensation process and subsequent decompensation process of the contralateral kidney. It was especially noticeable when analyzing the asymmetry of the fixation of the radiopharmaceutical in the functioning kidney parenchyma, depending on the degree of the disease progression.&#x0D; 20 patients with kidney cancer underwent osteoscintigraphy for the complete diagnosis to be established according to TNM. The following changes were detected: the presence of heterogeneous focal (17,8% of the cases) and multifocal (7,1% of the cases) distribution of the radiopharmaceutical.&#x0D; Conclusions. Performing a multi-target scintigraphy with 99mТс-MDP (phosphates) in malignant process in the kidney allows the functional capacity of the kidneys and the presence of the secondary lesion of the bones to be assessed in one exami- nation. Besides reducing radiation burden on the patient (one examination instead of two), it is also economically beneficial.

Lifetime body weight trajectories and risk of renal cell cancer: a large US prospective cohort study.

Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess bodyweight. Using the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N=138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: 1) BMI at specific ages; 2) adulthood BMI trajectories; 3) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and 4) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC. A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared to individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight (HR:1.49, 95%CI:1.19,1.87), from normal BMI to obesity (HR:2.22, 95%CI:1.70,2.90), and from overweight to obesity (HR:2.78, 95%CI:1.81,4.27). Compared to individuals who were never overweight (WYO=0), elevated HRs were observed among individuals who experienced low (HR:1.31, 95%CI:0.99,1.74), medium (HR:1.57, 95%CI:1.20,2.05), and high (HR:2.10, 95%CI:1.62,2.72) WYO tertile. Weight gain of ≥10kg was associated with increased RCC incidence for each age span. Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk. It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk.

Reduced number of IFN-γ producing cells in peripheral blood is a biomarker for patients with renal cell carcinoma.

Renal cell cancer (RCC) is the most lethal of all the common urologic cancers and constitutes 2.2% of all malignancy diagnoses. The incidence of RCC has been steadily increasing in recent decades. The classic risk factors of RCC include smoking, hypertension, obesity, genetics, and genetic mutations. Recent studies also revealed that RCC was an immunogenic tumor and affected by host immune status. Among the pan‐cance, RCC presented with the highest degree of immune infiltration, indicating RCC patients might benefit from immunotherapy. A new immune classification of RCC has been developed by Su et al. based on tumor‐infiltrating lymphocytes to guide clinical practice. However, these studies mainly focus on biomarkers derived from tumor microenvironment (TME), the biomarkers based on peripheral blood samples to RCC have rarely been described. We collected peripheral blood samples from RCC patients and their matched healthy controls and detected the number of IL‐2 and IFN‐γ producing cells by implementing an enzyme‐linked immunospot (ELISPOT) assay. This is the first study to report blood‐based immune biomarkers for RCC using an ELISPOT assay. Our results suggested the frequency of IFN‐γ producing cells but not IL‐2 producing cells was associated with RCC risk. These findings warrant further validation in larger prospective studies.

Gender Differences in Incidence, Diagnosis, Treatments, and Outcomes in Clinically Localized Bladder and Renal Cancer

ObjectiveTo review differences in bladder and renal cell cancer (RCC) incidence, diagnosis, treatment, and outcomes between men and women, and to summarize the evidence that explains these differences. MethodsA review of the current literature was performed using PubMed and Google Scholar. ResultsThe incidence of bladder cancer and RCC is higher in men. Historically higher smoking rates among men explain some but not all of the difference in incidence. Hormonal and genetic factors also contribute. In bladder cancer, the androgen receptor and estrogen receptor beta have been associated with gender and tumor characteristics. In RCC the relationships are less well defined. In both bladder cancer and RCC, differences in gene mutation patterns among men and women, particularly among genes located on the X-chromosome, have also been identified. Differences in the work-up and treatment of men and women with bladder cancer and RCC also contribute to gender disparities. ConclusionResearch to better delineate how the hormonal axis and genetics contribute to disparities in bladder cancer and RCC incidence and outcomes will allow for more individualized medicine. Appreciation of barriers to diagnosis and treatment will identify opportunities to improve patient care.

Renal Cell Cancer: Clinicopathological Profile and Survival Outcomes

AbstractBackground: The incidence of renal cell cancer (RCC) is increasing worldwide. However, scant information is available from the Indian subcontinent regarding its clinicopathological characteristics and survival outcomes. We retrospectively analyzed data of patients suffering from RCC at our center over the last one decade (2004–2013) to generate information on these aspects. Materials and Methods: Case records of 423 patients treated between 2004 and 2013 were retrospectively analyzed. Baseline characteristics, histopathological information, and survival outcomes were assessed. Overall survival was calculated from the time of diagnosis to death due to any cause. Results: The median age was 52 years (range: 18–87 years). Male: female ratio was 3.5:1. The median duration of symptoms was 3 months (range: 0–24 months). Thirty-five patients (8.3%) were detected in asymptomatic state. The most common symptom was hematuria (53.2%) followed by flank pain (46.3%). The most common histology was clear cell subtype (71.4%). Two hundred and ninety-three (69.3%) patients presented with nonmetastatic disease whereas 130 (30.7%) had upfront metastatic disease. Five-year survival in Stages 1, 2, 3, and 4 was 92.7%, 72.9%, 54.6%, and 11.5%, respectively. Conclusion: Younger age, higher male–female ratio, lower proportion of asymptomatic patients, higher proportion of advanced stage at diagnosis, and lower stage-wise survival were some of the key findings.

A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer

Clear cell renal cell carcinoma (ccRCC) is the most common and most aggressive form of renal cell cancer (RCC). The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1, as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways.

Do programmed death 1 (PD-1) and its ligand (PD-L1) play a role in patients with non-clear cell renal cell carcinoma?

Clinical trials targeting programmed death 1 (PD-1) and its ligand PD-L1 (PD-L1) for metastatic renal cell cancer (RCC) are ongoing. The aim of this study is to validate their roles as prognostic markers in non-clear cell (non-cc) RCC. Sixty-four non-cc RCC tissue specimens were collected from patients undergoing renal tumor surgery. Expressions of biomarkers were assessed using immunohistochemistry and compared with clinical characteristics. Survival analyses were performed with a median follow-up of 77.5 (range: 0-176) months. No significant correlations were found for PD-1(+) tumor-infiltrating mononuclear cells (TIMC) or PD-L1(+) expression and clinical attributes in patients with non-cc RCC. Kaplan-Meier analysis revealed no differences in 5- and 10-year cancer-specific survival (CSS) for PD-1(-) TIMC compared to PD-1(+) TIMC (71.4 and 63% versus 72.2 and 61.9%; p=0.88). Intratumoral expression of PD-L1 did not appear to influence the 5- and 10-year CSS significantly, even though a trend was identified (68 and 53.6% versus 80.1 and 75.7%; p=0.08). In multivariate analysis, neither PD-1(+) TIMC nor intratumoral PD-L1(+) expression proved to be independent predictors of CSS (p=0.99 and p=0.68, respectively). Our study demonstrates that PD-1(+) TIMC and intratumoral PD-L1(+) expression did not significantly impact tumor aggressiveness or clinical outcome in non-ccRCC specimens. Due to rare incidence of non-cc RCC in particular according to PD-L1 expression, further analyzes are warranted.

Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database

The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort. We queried the SEER (Surveillance, Epidemiology and End Results) 18-registry database for all patients 20 years old or older who were surgically treated for renal cell carcinoma between 2001 and 2008. Patients with unknown race, grade, stage or histology and those with multiple tumors were excluded from study. Four cohorts were created by dividing patients by gender, including 1,202 females and 1,715 males younger than 40 years old, and 18,353 females and 30,891 males 40 years old or older. Chi-square analysis was used to compare histological distributions between the cohorts. While clear cell carcinoma was still the most common renal cell cancer subtype across all genders and ages, chromophobe renal cell cancer was the most predominant type of nonclear renal cell cancer histology in young females, representing 62.3% of all nonclear cell renal cell cancers (p <0.0001). In all other groups papillary renal cell cancer remained the most common type of nonclear renal cell cancer. It is possible that hormonal factors or specific pathway dysregulations predispose chromophobe renal cell cancer to develop in younger women. We hope that this work provides some new observations that could lead to further studies of gender and histology specific renal tumorigenesis.

Renal cell carcinoma: Review of etiology, pathophysiology and risk factors.

The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways.

Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition.

Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 and 2000. Until December 2008, 691 RCC cases have been identified. Meat and fish consumption was assessed at baseline using country-specific dietary assessment instruments; 24-hour recalls were applied in an 8% subsample for calibration purposes. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Women with a high consumption of red meat (HR = 1.36, 95% CI 1.14-1.62; calibrated, per 50 g/day) and processed meat (HR = 1.78, 95% CI 1.05-3.03; calibrated, per 50 g/day) had a higher risk of RCC, while no association existed in men. For processed meat, the association with RCC incidence was prominent in premenopausal women and was lacking in postmenopausal women (p interaction = 0.02). Neither poultry nor fish consumption were statistically significantly associated with the risk of RCC. The results show a distinct association of red and processed meat consumption with incident RCC in women but not in men. A biological explanation for these findings remains unclear.

Abstract LB-279: Nonsteroidal anti-inflammatory drug (NSAID) use and risk of lethal renal cell carcinoma

Abstract Background: Studies suggest that non-steroidal anti-inflammatory drug (NSAID) use may increase risk of renal cell cancer (RCC), but the relationship to the lethal form of RCC remains unknown. Methods: We examined the relationship between NSAID use and RCC risk in two large prospective cohorts: the Nurses’ Health Study and the Health Professionals Follow-up Study. Use of aspirin and other NSAIDs was ascertained in 1990 in the Nurses’ Health Study and in 1986 in the Health Professionals Follow-up Study, and every 2 years thereafter. We evaluated baseline use and duration of NSAID use. We defined the lethal form of RCC as RCC that resulted in death due to the disease. Results: During follow-up of 18 years among 77,524 women and 20 years among 49,403 men, we documented 364 cases of RCC, of which 102 were fatal. Regular use of non-aspirin NSAIDs was associated with an increased overall RCC risk; there was a dose-response relationship between duration of non-aspirin NSAID use and RCC risk; compared with non-regular use, the pooled multivariable relative risks (RRs) were 0.78 (95% CI, 0.58-1.06) for use of less than 4 years, 1.29 (95% CI, 0.95-1.74)) for 4 to less than 10 years, and 2.21 (95% CI 1.39-3.49) for use for 10 or more years (P for trend, 0.0006). Furthermore, non-aspirin NSAID users of 4-10 years (pooled multivariable RR 3.13, 95% CI 1.70-5.77) and more than 10 years (pooled multivariable RR 7.23, 95% CI 2.51-20.83) had a significantly increased risk of lethal RCC. Aspirin use was not associated with increased risk of overall (pooled multivariable RR 1.07, 95% CI 0.84-1.34) or lethal RCC (pooled multivariable RR 1.59, 95% CI 0.85-2.96). Conclusion: Our prospective data suggest that non-aspirin NSAID use is associated with an increased incidence of RCC, especially the lethal form of RCC. Citation Format: Mark A. Preston, Jed-sian Cheng, Glen Barrisford, Alex Sanchez, Adam S. Feldman, Dayron Rodriguez, Toni K. Choueiri, Meir Stampfer, Walter C. Willett, Eunyoung Cho. Nonsteroidal anti-inflammatory drug (NSAID) use and risk of lethal renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-279. doi:10.1158/1538-7445.AM2014-LB-279

Commentary on “Predicted plasma 25-hydroxyvitamin D and risk of renal cell cancer.” Joh HK, Giovannucci EL, Bertrand KA, Lim S, Cho E, Department of Medicine, Seoul National University College of Medicine, Seoul, South Korea.: J Natl Cancer Inst 2013; 105(10):726–32. [Epub 2013 Apr 8]. doi: 10.1093/jnci/djt082.

BackgroundAlthough the kidney is a primary organ for vitamin D metabolism, the association between vitamin D and renal cell cancer (RCC) remains unclear. MethodsWe prospectively evaluated the association between predicted plasma 25-hydroxyvitamin D [25(OH)D] and RCC risk among 72,051 women and 46,380 men in the period from 1986 to 2008. Predicted plasma 25(OH)D scores were computed using validated regression models that included major determinants of vitamin D status (race, ultraviolet B flux, physical activity, body mass index, estimated vitamin D intake, alcohol consumption, and postmenopausal hormone use in women). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. All statistical tests were two-sided. ResultsDuring 22 years of follow-up, we documented 201 cases of incident RCC in women and 207 cases in men. The multivariable hazard ratios between extreme quintiles of predicted 25(OH)D score were 0.50 (95% CI = 0.32 to 0.80) in women, 0.59 (95% CI = 0.37 to 0.94) in men, and 0.54 (95% CI = 0.39 to 0.75; P trend<.001) in the pooled cohorts. An increment of 10ng/mL in predicted 25(OH)D score was associated with a 44% lower incidence of RCC (pooled HR = 0.56, 95% CI = 0.42 to 0.74). We found no statistically significant association between vitamin D intake estimated from food-frequency questionnaires and RCC incidence. ConclusionHigher predicted plasma 25(OH)D levels were associated with a statistically significantly lower risk of RCC in men and women. Our findings need to be confirmed by other prospective studies using valid markers of long-term vitamin D status.

Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients with metastatic renal cell carcinoma.

BackgroundThe incidence of renal cell cancer (RCC) has been increasing for the past decade, and the 5-year survival for patients with metastatic RCC (mRCC) is rather low. Everolimus (RAD001), a new inhibitor for mammalian target of rapamycin (mTOR), is generally well tolerated, and demonstrates clinical benefit to patients with anti-VEGF-refractory mRCC. However, factors for selection of patients who may benefit from everolimus remain largely unknown. Here we aimed to explore potential molecular indicators for mRCC patients who may benefit from everolimus treatment.MethodsParaffin-embedded tumor tissue specimens derived from 18 mRCC patients before everolimus treatment, who participated the phase 1b trial of everolimus in VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI)-refractory Chinese patients with mRCC (clinicaltrials.gov, NCT01152801), were examined for the expression levels of phosphorylated AKT, mTOR, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4EBP1) and 40S ribosomal protein S6 (S6RP) by immunohistochemistry. Clinical benefit rate (complete response [CR], partial response [PR], plus stable disease [SD] ≥ 6 months) and progression-free survival time (PFS) were correlated with expression levels of these mTOR-associated molecules.ResultsIn these 18 patients, there were 1 PR, 15 SDs (including 9 SDs ≥ 6 months), and 2 progressive diseases (PD). The clinical benefit rate (CBR) was 55.6% (10/18), and the median PFS time was 8.4 months. Patients with positive expression of phospho-mTOR showed a better CBR (71.4% versus 0%, P = 0.023) and PFS time (11.3 versus 3.7 months, P = 0.001) than those patients with negative expression. The median PFS of patients with positive phospho-S6RP expression was longer (11.3 versus 3.7 months, P = 0.002) than that of patients negative for phospho-S6RP expression. However, expression levels of phospho-4EBP1 and phospho-AKT were unassociated to efficacy of everolimus treatment with respect to CBR and PFS. Co-expression of phosphorylated mTOR, S6RP and/or 4EBP1 may improve the predictive value of the biomarkers for patients treated with everolimus.ConclusionsThe expression levels of phospho-mTOR and phospho-S6RP may be potential predictive biomarkers for efficacy of everolimus in patients with mRCC. Combining examinations of phosphorylated mTOR, S6RP and/or 4EBP1 may be a potential strategy to select mRCC patients sensitive to mTOR inhibitor treatment.

Predicted Plasma 25-Hydroxyvitamin D and Risk of Renal Cell Cancer

Although the kidney is a primary organ for vitamin D metabolism, the association between vitamin D and renal cell cancer (RCC) remains unclear. We prospectively evaluated the association between predicted plasma 25-hydroxyvitamin D [25(OH)D] and RCC risk among 72,051 women and 46,380 men in the period from 1986 to 2008. Predicted plasma 25(OH)D scores were computed using validated regression models that included major determinants of vitamin D status (race, ultraviolet B flux, physical activity, body mass index, estimated vitamin D intake, alcohol consumption, and postmenopausal hormone use in women). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. All statistical tests were two-sided. During 22 years of follow-up, we documented 201 cases of incident RCC in women and 207 cases in men. The multivariable hazard ratios between extreme quintiles of predicted 25(OH)D score were 0.50 (95% CI = 0.32 to 0.80) in women, 0.59 (95% CI = 0.37 to 0.94) in men, and 0.54 (95% CI = 0.39 to 0.75; P trend < .001) in the pooled cohorts. An increment of 10 ng/mL in predicted 25(OH)D score was associated with a 44% lower incidence of RCC (pooled HR = 0.56, 95% CI = 0.42 to 0.74). We found no statistically significant association between vitamin D intake estimated from food-frequency questionnaires and RCC incidence. Higher predicted plasma 25(OH)D levels were associated with a statistically significantly lower risk of RCC in men and women. Our findings need to be confirmed by other prospective studies using valid markers of long-term vitamin D status.

Comparision of histologic distribution of RCC in young and older patients: Results from the SEER database.

419 Background: Renal cell cancer (RCC) incidence is relatively low in younger patients, encompassing 3-5% of all RCC tumors. These tumors tend to be due to hereditary syndromes and genetic mutations that predispose to cancer development. Patients with hereditary renal cancer (HRC) are at a higher risk of multiple tumors and bilateral disease. We hypothesize that there is a difference in histologic distribution in the younger patients and that the younger distribution contains more aggressive histologic subtypes. Methods: SEER 18-registries database was queried for all patients ≥20 years old that were surgically treated for renal cell carcinoma between the years 2001 and 2008. Patients with unknown race, grade, stage, or histology were excluded from the study. Histologies selected were clear cell, papillary, chromophobe, sarcomatoid, and collecting duct. Three cohorts were created with the ages 20-44, 45-64, and ≥65 year olds that contained 3,926, 19,661, and 16,323 patients respectively. Chi-square analysis was used to compare the histologic distributions between the cohorts. Results: There was no difference in the incidence of clear cell RCC between the three cohorts (p = 0.63). The histology distribution was not different in the 45-64 year olds compared to those ≥65 (p = 0.47). The non-clear cell histologies were different between the 3 age groups (p &lt; 0.001). There were a larger percentage of patients in the younger patients that had chromophobe tumors compared to all non-clear cell histologies (p&lt; 0.001). Conclusions: The difference in the non-clear cell histologic distribution between the groups is most likely due to genetic mutations predisposing these patients to chromophobe RCC. There has been limited data on HRCs, due in large part to its low incidence. Although the HRCs are known to have a most common histology, it is likely that this information is incomplete, as younger patients have undiagnosed genetic mutations that led to development of chromophobe tumors. [Table: see text]

Adolescent Obesity and Paternal Country of Origin Predict Renal Cell Carcinoma: A Cohort Study of 1.1 Million 16 to 19-Year-Old Males

The incidence of renal cell carcinoma has increased in recent decades, particularly among middle-aged adults. Early precursors of renal cancer remain unclear. We evaluated the association of body mass index and height determined in late adolescence, and paternal or grandpaternal country of origin with the risk of renal cell carcinoma. Health related data on 1,110,835 males at ages 16 to 19 years who were examined for fitness for military service between 1967 and 2005 were linked to the Israel National Cancer Registry in this nationwide, population based cohort study. We used Cox proportional hazards modeling to estimate the HR of renal cell carcinoma associated with birth year, body mass index, height, father country of origin and socioeconomic indicators. During 19,576,635 person-years of followup renal cancer developed in 274 examinees. Substantial excess risk was conferred by a body mass index of greater than 27.5 kg/m(2) compared to less than 22.5 kg/m(2) (HR 2.43, 95% CI 1.54-3.83, p <0.0001). Asian or African origin was protective compared to European origin (African origin HR 0.67, 95% CI 0.49-0.92). Overweight in late adolescence is a substantial risk factor for renal cell carcinoma. European origin is independently associated with excess risk and it persists among Israeli born males. Preventing childhood obesity may be a promising target for decreasing the burden of renal cancer.

ABO blood group and risk of renal cell cancer

Background: The genetic determinants of sporadic renal cell cancer (RCC) are largely unknown. Previous studies have suggested associations between ABO blood group and risk of various cancers. However, its relationship to RCC remains unclear and no prospective data are available. Methods: We prospectively followed up 77,242 women in the Nurses’ Health Study and 30,071 men in the Health Professionals Follow-Up Study from 1996 to 2008. The information on the ABO blood group was collected from participants’ self-reports in 1996. Incidence of pathology-confirmed RCC was compared using hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards models. Results: During 12years of follow-up, 163 cases of incident RCC were documented in women and 88 cases in men. The multivariate HRs between non-O blood group (combined group of A, AB, and B) vs. blood group O were 1.51 (95% CI 1.09–2.09) in women, 1.08 (95% CI 0.70–1.66) in men, and 1.32 (95% CI 0.95–1.82) in the pooled cohorts. The associations between ABO blood group and RCC were consistent across strata of known risk factors for RCC including age, obesity, smoking, and history of hypertension (Pinteraction≥0.32). Conclusions: We found a suggestive non-significant association between non-O blood group and increased risk of RCC in the pooled cohorts of men and women, and this association was significant in women. Our findings need to be replicated by other prospective studies.

Histopathology of Surgically Treated Renal Cell Carcinoma: Survival Differences by Subtype and Stage

Previous studies of the impact of renal cell carcinoma histopathology on survival are conflicting and generally limited to institutional analyses. Thus, we determined the role of renal cell carcinoma histopathology on the stage specific survival rate in a large population based cohort. We used the 2000 to 2005 National Cancer Institute SEER (Surveillance, Epidemiology and End Results) database to identify 17,605 patients who underwent surgery for renal cell carcinoma and met study inclusion criteria. Patients were stratified by histological subtype (clear cell, papillary, chromophobe, collecting duct and sarcomatoid differentiation) and pathological stage. We performed Cox proportional hazard modeling and Kaplan-Meier survival analysis to determine overall and cancer specific survival. Patients with papillary and chromophobe pathology were less likely to present with T3 or greater disease (17.6% and 16.9%, respectively) while patients with collecting duct and sarcomatoid variants were more likely to present with T3 or greater disease (55.7% and 82.8%, respectively) compared to those with clear cell histology (p <0.001). On multivariate analysis histology was significantly associated with overall and cancer specific survival. Patients with chromophobe pathology had improved survival (HR 0.56, 95% CI 0.40-0.78) while those with collecting duct and sarcomatoid variants had worse survival (HR 2.07, 95% CI 1.44-2.97 and 2.26, 95% CI 1.93-2.64, respectively). Renal cell carcinoma histological subtype predicts overall and cancer specific survival. Patients with collecting duct and sarcomatoid variants of renal cell carcinoma have poor survival, even those who present with low stage disease. These data suggest inherent differences in renal cell carcinoma biology and may ultimately form the basis of future histologically targeted therapies.