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1.  Application of the revised Tumour Node Metastasis (TNM) staging system of clear cell renal cell carcinoma in eastern China: advantages and limitations 
Asian Journal of Andrology  2013;15(4):550-557.
This study was designed to evaluate whether the revised 2010 Tumour Node Metastasis (TNM) staging system could lead to a more accurate prediction of the prognosis of renal cell carcinoma (RCC) patients. A total of 1216 patients who had undergone radical nephrectomy or partial nephrectomy for RCC from 2003 to 2011 were enrolled. All of the patients had pathologically confirmed clear cell RCC (ccRCC). All cases were staged by both the 2002 and 2010 TNM staging systems after pathological review, and survival data were collected. Univariate and multivariate Cox regression models were used to evaluate cancer-specific survival (CSS) and progression-free survival (PFS) after surgery. Continuous variables, such as age and tumour diameter, were calculated as mean values and standard deviations (s.d.) or as median values. Survival was calculated by the Kaplan–Meier method, and the log-rank test assessed differences between groups. Statistically significant differences in CSS and PFS were noted among patients in T3 subgroups using the new 2010 staging system. Therefore, the revised 2010 TNM staging system can lead to a more accurate prediction of the prognosis of ccRCC patients. However, when using the revised 2010 staging system, we found that more than 92% of patients (288/313) with T3 tumours were staged in the T3a subgroup, and their survival data were not significantly different from those of patients with T2b tumours. In addition, T2 subclassification failed to independently predict survival in RCC patients.
doi:10.1038/aja.2012.161
PMCID: PMC3739222  PMID: 23564046
kidney neoplasm; prognosis; renal cell carcinoma; TNM stage
2.  RISK OF METASTATIC RENAL CELL CARCINOMA ACCORDING TO TUMOR SIZE 
The Journal of urology  2009;182(1):41-45.
Purpose
Recent evidence suggests significantly discordant findings regarding tumor size and the risk of metastases in renal cell carcinoma (RCC). Herein, we present our experience with RCC and evaluate the association between tumor size and risk of metastases in a large cohort of patients.
Methods
Using our prospectively maintained nephrectomy database, we identified 2,691 patients treated surgically for a sporadic renal cortical tumor between 1989 and 2008. Associations between tumor size and synchronous metastases at presentation (M1 RCC) were evaluated with logistic regression models while metastases-free survival following surgery was estimated using the Kaplan-Meier method for 2,367 patients who did not present with M1 RCC and who were followed postoperatively.
Results
Among the 2,691 patients, 162 presented with metastatic RCC. Only 1 of 781 patients with a tumor <3cm had M1 RCC at presentation and tumor size was significantly associated with metastases at presentation (odds ratio 1.25 for each 1cm increase, p<0.001). Among the 2,367 patients who did not present with metastases, 171 developed metastatic disease during a median follow-up of 2.8 years. In this group, only 1 of the 720 patients with RCC <3cm developed a de novo metastases during follow-up. Metastases-free survival was significantly associated with tumor size (hazard ratio 1.24 for each 1cm increase, p<0.001).
Conclusion
In our experience, tumor size is significantly associated with synchronous metastases and asynchronous metastases following nephrectomy. Our results suggest that risk of metastatic disease for patients with tumors <3cm is negligible.
doi:10.1016/j.juro.2009.02.128
PMCID: PMC2735023  PMID: 19450840
Kidney neoplasms; Nephrectomy; Carcinoma; renal cell; Survival; Treatment outcome
3.  Age at diagnosis is a determinant factor of renal cell carcinoma–specific survival in patients treated with nephrectomy 
Objective
Based on combined data for 4880 patients, 2 previous studies reported that advanced age is a predictor of increased renal cell carcinoma–specific mortality (RCC-SM). We explored the effect of age in cubic spline analyses to identify the age groups with the most elevated risk for renal cell carcinoma (RCC).
Methods
Our study included 3595 patients from 14 European centres who had partial or radical nephrectomies. We used the Kaplan–Meier method to compile life tables, and we performed Cox regression analyses to assess RCC-SM. Covariates included age at diagnosis, sex, TNM (tumour, node, metastasis) stage, tumour size, Fuhrman grade, symptom classification and histological subtype.
Results
Age ranged from 10 to 89 (mean 63, median 67) years. The median duration of follow-up was 2.9 years. The median survival for the cohort was 13.4 years. Stage distribution was as follows: 1915 patients (53.3%) had stage I disease, 388 (10.8%) had stage II, 895 (24.9%) had stage III and 397 (11.0%) had stage IV disease. In multivariate analyses, we coded age at diagnosis as a cubic spline, and it achieved independent predictor status (p < 0.001). The risk of RCC-SM was lowest among patients younger than 50 years. We observed an increase in RCC-SM until the age of 50, at which point the level of risk reached a plateau. We observed a second increase among patients aged 75–89 years. We found similar patterns when we stratified patients according to the 2002 American Joint Committee on Cancer (AJCC) stages.
Conclusion
The effect of age shows prognostic significance and indicates that follow-up and possibly secondary treatments might need to be adjusted according to the age of the patient.
PMCID: PMC2593600  PMID: 19066680
4.  Association of Abnormal Preoperative Laboratory Values with Survival After Radical Nephrectomy for Clinically Confined Clear Cell Renal Cell Carcinoma 
Urology  2008;71(2):278-282.
Objectives
To determine whether preoperative laboratory values are independently associated with death from clinically confined clear cell renal cell carcinoma (RCC) after radical nephrectomy.
Methods
We identified 1707 patients with clinically confined (pNx/pN0, pM0), unilateral, sporadic clear cell RCC treated with radical nephrectomy between 1970 and 2002. Associations of abnormal preoperative laboratory values including hypercalcemia, anemia, elevated erythrocyte sedimentation rate (ESR), and elevated alkaline phosphatase with death from RCC were evaluated using Cox proportional hazards regression models, both univariately and multivariately by adjusting for known prognostic features of the 2002 primary tumor classification, tumor size, nuclear grade, and coagulative tumor necrosis.
Results
At last follow-up, 1009 patients had died, including 425 who died from RCC at a median of 3.0 years after surgery (range, 0 to 26 years). Even after adjusting for known prognostic features, 9% of patients with preoperative hypercalcemia exhibited significantly increased likelihood of dying from RCC compared with patients with normal or lower levels of serum calcium (relative ration [RR] 1.64; P = 0.002). Similarly, preoperative anemia (35% of patients; RR 1.27; P = 0.026) and elevated ESR (44% of patients; RR 1.66; P = 0.003) portended an increased risk of death from RCC even after multivariate adjustment.
Conclusions
Abnormal preoperative laboratory values including hypercalcemia, anemia, and elevated ESR are independently associated with increased risk of cancer-specific death from clinically confined clear cell RCC. Consideration of these variables in future models may improve prognostic accuracy. We believe these factors should be routinely assessed and included in prospective studies of outcome in RCC patients.
doi:10.1016/j.urology.2007.08.048
PMCID: PMC2789389  PMID: 18308103
5.  Survival, Classifications, and Desmosomal Plaque Genes in Non-Small Cell Lung Cancer 
Novel biomarkers are required to improve prognostic predictions obtained with lung cancer staging systems. This study of 62 surgically-treated Non-Small Cell Lung Cancer (NSCLC) patients had two objectives: i) to compare the predictive value of T-stage classifications between the 6th and 7th editions of the Tumor, Node, and Metastasis staging system (TNM); and ii) to examine the association of Pkp1 and/or Krt15 gene expression with survival and outcomes. Multivariate and Kaplan-Meier survival analyses were performed, examining the relationship of survival with T-stage, recurrence, and TNM-stage (by each TNM edition) and with the single/combined expression of Pkp1 and/or Krt15 genes. Five-year survival rates only significantly differed as a function of T-stage in patients without recurrence when estimated using the 6th edition of the TNM classification and only in patients in pathologic TNM-stage IA using the 7th. Overall survival for patients with elevated expression of both genes was 13.5 months in those with adenocarcinoma and 34.6 months in those with squamous cell carcinoma. Overall survival was 30.4 months in patients with Pkp1 gene upregulation and 30.9 months in those with Krt15 gene upregulation. In conclusion, survival estimations as a function of T-staging differed between the 6th and 7th editions of TNM. Overall survival differed according to the expression of Pkp1 and/or Krt15 genes, although this relationship did not reach statistical significance.
doi:10.7150/ijms.5747
PMCID: PMC3714393  PMID: 23869193
Survival; adenocarcinoma; squamous cell-carcinoma; non-small cell lung cancer; desmosomal plaque
6.  Prognostic factors in T3b renal cell carcinoma 
World journal of urology  2008;27(1):75-79.
Objectives
We reviewed our patients with pathologic T3b renal cell carcinoma (RCC) to determine which factors influenced survival in this high risk patient group.
Methods
From April 1988 to August 2006, 722 patients underwent nephrectomy for RCC at Vanderbilt University. 128 patients (17%) had T3b disease by 2002 AJCC TNM staging criteria. 31 (24%) of these patients had known metastases at the time of nephrectomy. Patient demographics, clinical, and pathological characteristics were collected.
Results
There were 95 men (74%) and 33 women (26%) whose median age was 64 years (range 35–87). Median follow-up was 25.2 months (0–124). Median follow-up among those still alive at last follow up was 45.8 months (2.4–114). For overall survival (OS), disease specific survival (DSS), and recurrence free survival (RFS), non-clear cell histology, grade, presence of sarcomatoid features, LN positive disease, presence of necrosis, positive margins, and metastasis present at the time of nephrectomy were all associated with worse outcomes. Race, gender, ASA class, age, and inferior vena cava (IVC) involvement were not associated with outcome. On multivariate analysis, metastasis at the time of nephrectomy, margin involvement, and the presence of necrosis were independently associated with decreased OS and DSS. The presence of necrosis and lymph node involvement were independent predictors of worse RFS.
Conclusions
Our data suggests that in patients with T3b RCC, the presence or absence of macroscopic necrosis should be included as part of the pathology report to help guide prognosis in this high risk patient group.
doi:10.1007/s00345-008-0358-9
PMCID: PMC2963091  PMID: 19039590
Kidney; Renal cell carcinoma; Thrombosis; Prognosis; Necrosis
7.  RENAL CELL CARCINOMA IN YOUNG AND OLD PATIENTS: IS THERE A DIFFERENCE? 
The Journal of urology  2008;180(4):1262-1266.
Purpose
Renal cell carcinoma (RCC) is rare in patients <40 years old and conflicting data regarding presentation and outcome are present in the literature. We reviewed our experience with young RCC patients comparing them to older counterparts.
Methods
We identified 1,720 patients 18-79 years old managed with partial or radical nephrectomy for RCC between 1989 and 2005. Patients were grouped according to age and outcome analyses were conducted.
Results
Among the 1,720 RCC patients, there were 89 (5%), 672 (39%), and 959 (56%) patients aged <40, 40-59, and 60-79 years old, respectively. There were no significant differences in sex, tumor size, TNM stage, or multifocality by age group. However, patients <40 years old were significantly more likely to present with symptomatic tumors (p=0.028). Additionally, there were significant differences in histology by age (p<0.001); chromophobe histology decreased while papillary histology increased with age. Despite similar tumor sizes in each age group, the percentage of patients treated with partial nephrectomy declined with age; 49% of patients <40 years old were treated with partial nephrectomy compared with 35% and 30% of patients aged 40-59 and 60-79 years old, respectively (p<0.001). With a median follow-up of 2.6 years (range 0-14.5), we did not observe a significant difference in cancer-specific survival according to age (p=0.17).
Conclusions
Younger RCC patients are more likely to have symptomatic tumors with chromophobe histology although prognosis appears similar across age groups. Older patients are more likely to be treated with radical nephrectomy and this requires careful scrutiny for current clinical practice.
doi:10.1016/j.juro.2008.06.037
PMCID: PMC2615196  PMID: 18707708
Carcinoma, renal cell; Kidney neoplasms; Age factors; Adenoma, chromophobe
8.  Modified primary tumour/vessel tumour/nodal tumour classification for patients with invasive ductal carcinoma of the breast 
British Journal of Cancer  2011;105(5):698-708.
Background:
We previously reported that the primary tumour/vessel tumour/nodal tumour (PVN) classification is significantly superior to the UICC pTNM classification and the Nottingham Prognostic Index for accurately predicting the outcome of patients with invasive ductal carcinoma of the breast in a manner that is independent of the nodal status and the hormone receptor status.
Methods:
The purpose of the present study was to compare the outcome predictive power of a modified PVN classification to that of the newly devised pathological UICC pTNM classification and the reclassified Nottingham Prognostic Index in a different group of patients with invasive ductal carcinoma (n=1042) using multivariate analyses by the Cox proportional hazard regression model.
Results:
The modified PVN classification clearly exhibited a superior significant power, compared with the other classifications, for the accurate prediction of tumour recurrence and tumour-related death among patients with invasive ductal carcinoma in a manner that was independent of the nodal status, the hormone receptor status, and adjuvant therapy status.
Conclusion:
The modified PVN classification is a useful classification system for predicting the outcome of invasive ductal carcinoma of the breast.
doi:10.1038/bjc.2011.279
PMCID: PMC3188933  PMID: 21811256
invasive ductal carcinoma; lymph vessel; blood vessel; lymph node; Nottingham Prognostic Index; prognosis
9.  Primary tumour–vessel tumour–nodal tumour classification for patients with invasive ductal carcinoma of the breast 
British Journal of Cancer  2005;92(5):847-856.
There are many studies that show biological differences between invasive ductal carcinoma (IDC) with and without nodal metastasis, but no prognostic classification taking into consideration any biological differences between them is currently available. We previously investigated the histological characteristics that play an important role in tumour progression of IDCs according to their nodal status, and a new prognostic histological classification, the primary tumour–vessel tumour–nodal tumour (PVN) classification, was devised based on the histological characteristics of IDCs with and without nodal metastasis. Multivariate analyses using the Cox proportional hazard regression models were used to compare the ability of the PVN classification to predict tumour recurrence and death in 393 IDC patients based on the following histological classifications: (1) the pTNM classification, (2) the Nottingham Prognostic Index, (3) the modified Nottingham Prognostic Index, and (4) the histologic grade. In IDCs without nodal metastasis, only the PVN classification significantly increased the hazard rates (HRs) of tumour recurrence and death (P<0.05), independent of the hormone receptor status. Similarly, in IDCs with nodal metastases, only the PVN classification significantly increased the HRs of tumour recurrence and death (P<0.05), independent of the hormone receptor status. We conclude that the PVN prognostic histological classification is the best classification available for IDC of the breast.
doi:10.1038/sj.bjc.6602353
PMCID: PMC2361891  PMID: 15756255
invasive ductal carcinoma; prognosis; histology; pTNM; Nottingham Prognostic Index; classification
10.  The impact of histology on survival for patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy 
Objective:
To evaluate the impact of histology on cancer-specific and overall survival for patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN).
Materials and Methods:
We retrospectively reviewed the data of 505 patients with mRCC who underwent CN at Mayo Clinic, Rochester, MN, USA, between 1970 and 2008. All specimen were re-reviewed by a single genitourinary pathologist. Survival was estimated using the Kaplan–Meier method and compared according to histology with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of histology with outcome.
Results:
Forty (8%) patients with non-clear cell histology and 465 (92%) patients with clear cell histology were identified. The median follow-up was 7.8 years. Metastatic non-clear cell histology was associated with a significantly older median age at nephrectomy (66 vs. 60 years; P = 0.002), larger median tumor size (11.5 vs. 9.2 cm; P = 0.02), and higher rate of lymph node involvement (50% vs. 16%; P < 0.001). No significant difference in 3-year cancer-specific survival (25% vs. 22%; P = 0.50) was noted between patients with clear cell and non-clear cell histology. On multivariate analysis, non-clear cell histology was not significantly associated with patients’ risk of death from cancer (HR 0.96; 95% CI 0.61, 1.51; P = 0.85).
Conclusions:
Non-clear cell histology was not independently associated with adverse survival for patients with mRCC undergoing CN. As such, we advocate that surgical resection should continue to be considered in the multimodal treatment approach to these patients, while additional efforts to risk stratify and optimize management in this setting remain necessary.
doi:10.4103/0970-1591.124204
PMCID: PMC3897051  PMID: 24497680
Histology; kidney cancer; metastasis; nephrectomy; renal cell carcinoma
11.  Diagnostic and Prognostic Role of Preoperative Circulating CA 15-3, CA 125, and Beta-2 Microglobulin in Renal Cell Carcinoma 
Disease Markers  2014;2014:689795.
CA 15-3, CA 125 and β-2 microglobulin are three common tumor markers currently used for diagnosis, prognosis, assessment of therapeutic response, and/or to evaluate recurrence in breast and ovarian cancer and malignant lymphoproliferative disorders, respectively. In the present prospective study we assessed the role of these three serum proteins as biomarkers for renal cell carcinoma (RCC), as well as any association between tumor marker levels and clinical-pathological parameters. CA 15-3, CA 125, and β-2 microglobulin were preoperatively measured in 332 patients who underwent nephrectomy for RCC. Estimates of cancer-specific survival (CSS) was calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS. Preoperatively, 35.2% (n = 117), 9.6% (n = 32) and 30.4% (n = 101) of the patients had abnormal levels of CA 15-3, CA 125 and β-2 microglobulin, respectively. Statistically significant differences resulted between CA 15-3, CA 125 and β-2 microglobulin values and tumor size, Fuhrman grade, presence of lymph node, and visceral metastases. CSS was significantly decreased for patients with high levels of CA 15-3, CA 125, and β-2 microglobulin (P < 0.0001, P < 0.0001, and P = 0.001, resp.). At multivariate analysis only age, the presence of visceral metastases, and high levels of CA 15-3 were independent adverse prognostic factors for CSS.
doi:10.1155/2014/689795
PMCID: PMC3947895
12.  Preoperative Erythrocyte Sedimentation Rate Independently Predicts Overall Survival in Localized Renal Cell Carcinoma following Radical Nephrectomy 
Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR) and overall survival in localized renal cell carcinoma (RCC) following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0 mm/hr), intermediate (20.1–50.0 mm/hr), and high risk (>50.0 mm/hr) groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI) survival was 44.1 (42.6–45.5) months, 35.5 (32.3–38.8) months, and 32.1 (25.5–38.6) months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649) and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228) increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC.
doi:10.1155/2012/524981
PMCID: PMC3414066  PMID: 22900160
13.  Cyclooxygenase-2 and p53 Expression as Prognostic Indicators in Conventional Renal Cell Carcinoma 
Yonsei Medical Journal  2005;46(1):133-140.
The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p=0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p<0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.
doi:10.3349/ymj.2005.46.1.133
PMCID: PMC2823039  PMID: 15744816
Cyclooxygenase-2; p53; prognosis; renal cell carcinoma
14.  Prognostic significance of CD45RO+ memory T cells in renal cell carcinoma 
British Journal of Cancer  2011;105(8):1191-1196.
Background:
Memory T cells are well known to have a critical role for host defense in humans. However, their role in actual human cancer remains largely unknown. In this study, we tried to reveal the clinical importance of tumour-infiltrating CD45RO+ memory T cells in renal cell carcinoma (RCC).
Methods:
We analysed 105 patients with RCC, who received radical or partial nephrectomy. Those were 65 in TNM stage I, 7 in stage II, 15 in stage III, and 18 in stage IV, respectively. CD45RO expression was evaluated by immunohistochemistry. CD4 and CD8 expressions were also systematically assessed in the same manner.
Results:
Patients with higher TNM stage or high nuclear grade were found to have higher densities of CD45RO. Furthermore, CD45RO status was positively correlated with preoperative C-reactive protein level. In prognostic analysis, CD45RO+lo patients had a significantly better prognosis than CD45RO+hi patients. There was also a significant difference between CD4+lo and CD4+hi groups, whereas no significant difference was observed in CD8 T-cell status. Finally, multivariate analysis revealed that CD45RO+ status was the independent prognostic factor for patient overall survival.
Conclusion:
CD45RO+ memory T-cell status has a significant independent prognostic value, indicating that the adaptive immune response is functionally critical in human RCC.
doi:10.1038/bjc.2011.368
PMCID: PMC3208496  PMID: 21934683
renal cell carcinoma; memory T cell; CD45RO; tumour-infiltrating lymphocytes; prognosis
15.  Radical or simple nephrectomy in localized renal cell carcinoma: what is a choice? 
Introduction
Renal cell carcinoma (RCC) accounts for approximately 3% of all adult malignancies. Surgery remains the only effective method of renal tumors treatment. In fact, for advanced RCC, radical nephrectomy (RN) should remain a standard treatment. However, in localized RCC (LRCC) a real increase of survival rates realized by RN compared with simple nephrectomy (SN) or organ-sparing surgery is discussable. The aim of our study was to assess the impact of nephrectomy type on the prognosis of LRCC treatment.
Material and methods
We analyzed the long-term outcomes of RN (n = 248 pts.) and SN (n = 170 pts.) in 418 pts. with LRCC. There were no significant statistical differences in tumor stages, age stratification or gender between these two groups. To compare the efficacy of RN and SN we determined overall survival (OS) and cancer-specific survival (CSS) rates in both divided groups. The 3-year OS in RN group was 93.1% vs. 91.8% in SN group.
Results
CSS rates after the same period were 96.8% vs. 94.7% respectively. The 5-year OS in RN group was 91.5% vs. 88.8% in SN group. After 5 years of follow-up, CSS in RN group was 94.4% vs. 92.4% in SN group. Type of nephrectomy does not influence on LRCC outcomes. The 3- and 5-year overall survival rates and cancer-specific survival rates in RN and SN group were almost identical.
Conclusion
Hence, if radical nephrectomy does not ensure better survival than simple nephrectomy, the expediency of vast surgery in localized RCC is doubtful.
doi:10.5173/ceju.2011.03.art12
PMCID: PMC3921726  PMID: 24578883
nephrectomy; localized renal cell carcinoma; overall survival; cancer-specific survival
16.  THE IMPACT OF COMORBIDITY ON OVERALL SURVIVAL IN PATIENTS SURGICALLY TREATED FOR RENAL CELL CARCINOMA 
Urology  2008;72(2):359-363.
Objectives
While the classification of cancer has traditionally focused on gross and microscopic characteristics of the tumor, overall health of a patient can impact survival. Since patients with renal cell carcinoma (RCC) often have other medical conditions, we explored the impact of preexisting medical disease on survival following radical and partial nephrectomy.
Methods
Between January 1995 and August 2003, comorbidity status of 697 nonmetastatic RCC patients who underwent radical or partial nephrectomy was prospectively coded using the Adult Comorbidity Evaluation-27. Histopathologic review of all slides was performed according to the 2004 World Health Organization scheme. Other variables analyzed include age, gender, ethnicity, pathologic stage, Fuhrman grade, and tumor size. The effect of these factors on overall survival (OS) was analyzed using Cox Proportional Hazards Regression.
Results
The median follow-up was 32.2 months for survivors and 36.5 months for all patients. OS rate at 1, 3, and 5 years was 92.0% (641 patients), 75.3% (525 patients) and 52.7% (367 patients). Univariate analyses demonstrated that age, comorbidity, tumor size, Fuhrman grade, and pathologic stage were significant predictors of OS. Multivariate analysis revealed that age (HR 1.42, 95% CI 1.10–1.82, p=0.0067), comorbidity (HR 1.37, 95% CI 1.16–1.63, p=0.0002), pathologic stage (HR 1.97, 95% CI 1.60–2.41, p<0.0001) and grade (HR 1.83, 95% CI 1.28–2.59, p=0.0008) predicted OS.
Conclusions
This study demonstrates that comorbidity is an independent prognostic factor for OS in RCC patients. Capturing comorbidity information using validated instruments can improve the preoperative evaluation of patients by providing more accurate prognostic information.
doi:10.1016/j.urology.2008.02.061
PMCID: PMC2570477  PMID: 18468663
17.  Comparison of Partial and Radical Nephrectomy for pT1b Renal Cell Carcinoma 
Korean Journal of Urology  2010;51(9):596-600.
Purpose
Partial nephrectomy (PN) for patients with T1a renal cell carcinoma (RCC) has increasingly become accepted, although its role for patients with T1b RCC remains controversial. We retrospectively evaluated and then compared the oncologic and functional outcomes of patients with pT1b RCC who were treated with PN or radical nephrectomy (RN).
Materials and Methods
A total of 70 patients who were diagnosed with pT1bN0M0 RCC between January 1995 and December 2004 were included. The 5-year overall survival (OS), the 5-year recurrence-free survival (RFS), and the 5-year cancer-specific survival (CSS) were compared between the groups. Preoperative and postoperative serum creatinine and estimated glomerular filtration rate (GFR) levels were analyzed to assess renal function.
Results
The 5-year OS (92.3% vs. 87.8%, p=0.501), RFS (92.3% vs. 77.8%, p=0.175), and CSS (92.3% vs. 94.5%, p=0.936) of the PN and RN groups were not statistically different. The proportion of patients with decreased renal function was lower in the PN group than in the RN group (PN=0% vs. RN=11.5%). The postoperative change in serum creatinine and the GFR 1 year after nephrectomy was higher in the RN group than in the PN group (PN=0.2±0.2, 12.1±9.1 vs. RN=0.3±0.5, 18.1±12.5), but there was no statistical difference.
Conclusions
There were no statistically significant differences in prognosis or renal function between patients treated with PN and those treated with RN for pT1b RCC. PN may be a useful treatment modality for patients with pT1b RCC.
doi:10.4111/kju.2010.51.9.596
PMCID: PMC2941807  PMID: 20856643
Nephrectomy; Prognosis; Renal cell carcinoma
18.  Prognostic Impact of Muscular Venous Branch Invasion in Localized Renal Cell Carcinoma 
The Journal of urology  2010;185(1):37-42.
Objective
Beginning with the 2002 AJCC staging system, renal sinus muscular venous branch invasion has prognostic equivalence with renal vein invasion (RVI) in renal cell carcinoma. To validate this presumed equivalence, we compared patients with isolated MVBI to those with RVI and to those without any confirmed vascular invasion.
Methods
From routine cataloging at Memorial Sloan-Kettering Cancer Center, we identified 500 patients who underwent partial or radical nephrectomy from 2003 to 2008. After excluding patients with metastasis or non-cortical RCC pathology, 85 patients with MVBI (+) were identified. Patients with pT1-2 MVBI (−) (n = 259) or RVI (+) (n = 71) disease served as comparison groups. A multivariable Cox model was used to control for tumor characteristics, using the Kattan RCC nomogram.
Results
In multivariable analysis, the risk of recurrence in the pT1-2 MVBI (−) group was lower than in the MVBI (+) group (HR 0.06, 95% CI 0.02–0.18; p <0.001). Patients with RVI (+) had similar recurrence rates to those with MVBI (+) (HR 0.80, 95% CI 0.39–1.65; p = 0.6). Overall survival rates were higher in the MVBI (−) group than in the other groups.
Conclusion
Patients with MVBI have inferior outcomes compared to those with pT1-2 disease. This confirms the adverse prognosis of MVBI and supports pathologic upstaging. The prognosis of MVBI is similar to that of RVI, although we can’t exclude the possibility of a difference. Our findings underscore the importance of close patient follow-up and careful pathologic assessment of the nephrectomy specimen.
doi:10.1016/j.juro.2010.08.084
PMCID: PMC3437930  PMID: 21074196
renal cell carcinoma; muscular venous branch invasion; vascular; prognosis; TNM stage
19.  Surgical resection for locally invasive renal cell carcinoma: Is it worthwhile? 
Background:
Many patients with renal cell carcinoma (RCC) present with disease involving the adjacent viscera. Although survival in such patients is poor, surgery remains the only proven modality of treatment. We describe our experience with radical nephrectomy for locally invasive RCC over a five-year period.
Study Design:
A retrospective analysis of the records of all patients who had undergone surgery for locally invasive RCC between January 1999 and December 2004 at our institute.
Materials and Methods:
During the study period, 102 patients with RCC underwent surgery at our institute, out of which 18 (17.6%) patients had adjacent organ involvement. The survival and outcomes in terms of symptom relief are described.
Statistical Analysis:
The survival rates were calculated by the Kaplan-Meier method using EGRET statistical software package.
Results:
Of the 18 patients, two patients had inoperable disease. Fifteen out of the 18 patients succumbed to their disease after a median period of 7.5 months. Three patients are still alive, having survived for 13, 16 and 25 months. Most patients derived considerable benefit with respect to relief of symptoms, which was long-lasting.
Conclusion:
For selected patients with locally invasive RCC, radical nephrectomy with en bloc resection of involved organs may provide the opportunity for long-term survival. In others, it may provide considerable symptomatic relief.
doi:10.4103/0970-1591.33444
PMCID: PMC2721599  PMID: 19718323
Locally invasive; radical nephrectomy; renal cell carcinoma
20.  Expression of Claudin-1 and -7 in Clear Cell Renal Cell Carcinoma and Its Clinical Significance 
Korean Journal of Urology  2011;52(5):317-322.
Purpose
We investigated the correlations between the expression of claudin-1 and claudin-7 in clear cell renal cell carcinoma (clear cell RCC) and clinical parameters.
Materials and Methods
The subjects of this study were 119 patients with confirmed clear cell RCC between January 2000 and December 2007. Their RCC tissues were immunohistochemically stained for claudin-1 and claudin-7. The correlations between the expression of claudin and parameters such as sex, age, body mass index (BMI), tumor size, TNM stage, Furhman nuclear grade, postoperative distant metastasis, and cancer-specific survival were analyzed.
Results
Among the total 119 subjects, claudin-1 was expressed in 18 (15.1%) and claudin- 7 in 31 (26.1%). Claudin-1 was expressed in patients who were older (p=0.007), who had a greater tumor size (p=0.001), who had a higher pathologic T stage (p=0.009), who had preoperative distant metastasis (p=0.035), and who had a higher Furhman nuclear grade (p=0.004). Claudin-7 was expressed only in patients who had a higher Furhman nuclear grade (p=0.031). The risk of postoperative distant metastasis was associated with the expression of claudin-1 (p<0.001) but not with the expression of claudin-7 (p=0.668). The expression of claudin-1 and -7 was not associated with cancer-specific survival (p>0.05).
Conclusions
In clear cell RCC, claudin-1 was expressed in patients who were older and who had a greater tumor size, who had higher T or M stages, and who had a higher Furhman nuclear grade. The expression of claudin-1 was associated with a higher risk of postoperative distant metastasis.
doi:10.4111/kju.2011.52.5.317
PMCID: PMC3106163  PMID: 21687390
Claudin 1; Claudin 7; Renal cell carcinoma
21.  C-reactive protein in patients with advanced metastatic renal cell carcinoma: Usefulness in identifying patients most likely to benefit from initial nephrectomy 
BMC Cancer  2012;12:337.
Objective
C-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied.
Patients and methods
We retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests.
Results
ROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (≥67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (≤18.0 mg/L, >18.0 and <67.0 mg/L, and ≥67.0 mg/L), ECOG PS (0, 1, and ≥2), and number of metastatic organ sites (0–1 and ≥2). The retrospective design is a limitation of this study.
Conclusion
Our study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC.
doi:10.1186/1471-2407-12-337
PMCID: PMC3487844  PMID: 22857740
C-reactive protein; Rena cell carcinoma; Prognosis
22.  Histopathological analysis of T1 renal cell carcinoma: Does presentation matter? 
Objectives:
To study the differences in the clinico-pathological features of incidental and symptomatic T1 renal cell carcinoma (RCC) and to see, particularly in T1b RCC, if symptomatic presentation has adverse pathological features concerning the oncological safety of elective nephron-sparing surgery (NSS) in this subgroup.
Materials and Methods:
Of 278 patients who underwent radical nephrectomy for RCC from January 1995 to January 2005, 70 had tumor size up to 7 cm (T1). They were categorized as incidental or symptomatic and as T1a or T1b tumors. Clinico-pathological features were compared between incidental (IRCC) and symptomatic (SRCC) groups. Tumors were analyzed using the 1997 TNM staging and Fuhrman's grade.
Results:
Of the 70 with T1 tumors, 24 had T1a (IRCC, 12 and SRCC, 12) and 46 had T1b tumors (IRCC, 27 and SRCC, 19). Clear cell was the commonest histology. In T1a cancers, though no significant difference in histopathological pattern and grade was seen between the incidental and symptomatic groups, symptomatic tumors had more papillary, mixed histopathological pattern and higher nuclear grade. Among T1b tumors, 14 had papillary and mixed histology, 12 (86%) of which were symptomatic (P= <0.0001). In T1b, 15 (79%) symptomatic had higher nuclear grade (G2-3) while 22 (81%) incidental had lower Fuhrman′s grade (P= <0.0001).
Conclusion:
Symptomatic T1b RCCs had higher nuclear grade and papillary histology. This difference was statistically significant. This may be relevant when considering elective NSS in symptomatic T1b disease.
doi:10.4103/0970-1591.44257
PMCID: PMC2684406  PMID: 19468506
Incidental; nephron-sparing surgery; renal cell carcinoma
23.  Autologous CIK Cell Immunotherapy in Patients with Renal Cell Carcinoma after Radical Nephrectomy 
Objective. To evaluate the efficacy of autologous cytokine-induced killer (CIK) cells in patients with renal cell carcinoma (RCC). Methods. 20 patients diagnosed with TNM stage I or II RCC were randomly divided into two groups, a CIK cell treatment group and a control group. The endpoint was progression-free survival (PFS) evaluated by Kaplan-Meier analyses. Results. CD3+, CD3+/CD8+, CD3+/CD4+, and CD3+/CD56+ levels increased after CIK cell culture (P < 0.01). The median PFS in CIK cell treatment group was significantly longer than that in control group (PFS, 32.2 months versus 21.6 months; log-rank, P = 0.032), all patients were alive during the course of followup, and there are no statistically significant differences between two groups in OS (log-rank, P = 0.214). Grade III or greater adverse events were not observed. Conclusions. CIK cells treatment could prolong survival in patients with RCC after radical nephrectomy and showed acceptable curative effect with potential enhancement of cellular immune function. This trial is registered with Clinicaltrials.gov NCT01799083.
doi:10.1155/2013/195691
PMCID: PMC3872096  PMID: 24382970
24.  A population-based study examining the effect of tyrosine kinase inhibitors on survival in metastatic renal cell carcinoma in Alberta and the role of nephrectomy prior to treatment 
Background
We performed a retrospective population-based study to assess the impact of tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients treated for metastatic renal cell carcinoma (mRCC) in Alberta, Canada and to assess the impact of nephrectomy on OS in patients treated with TKIs.
Methods
We identified 134 patients who began taking a TKI between December 2003 and June 2007 for mRCC in Alberta. We compared survival in this group to that in an earlier cohort of 141 patients treated with interferon-α (IFN-α) between May 1995 and March 2003. We used the Kaplan–Meier method to determine OS, and we used a Cox proportional hazards model to determine hazard ratios (HRs) and confidence intervals (CIs). We performed multivariate analysis to assess the impact of neprhectomy on OS.
Results
Of the 134 patients treated with TKIs, 81 received treatment in the first-line setting, whereas 53 received treatment after prior IFN-α therapy. All 141 patients from the IFN-α cohort received treatment in the first-line setting. Patients treated with TKIs had an improved OS compared with the IFN-α cohort (HR 0.61, 95% CI 0.45–0.83, p = 0.001). The median OS was 18 months in the TKI group and 10 months in the IFN-α group. The benefit of TKIs was confined to favourable and intermediate risk groups according to the Memorial Sloan-Kettering Cancer Center prognostic model. Prior nephrectomy was associated with improved OS in the TKI cohort, independent of other prognostic factors.
Conclusion
Tyrosine kinase inhibitors improve OS compared with IFN-α in mRCC. In patients treated with TKIs, prior nephrectomy is associated with improved survival independent of other prognostic variables.
PMCID: PMC2723887  PMID: 19672439
25.  Which Is a More Accurate Predictor in Colorectal Survival Analysis? Nine Data Mining Algorithms vs. the TNM Staging System 
PLoS ONE  2012;7(7):e42015.
Objective
Over the past decades, many studies have used data mining technology to predict the 5-year survival rate of colorectal cancer, but there have been few reports that compared multiple data mining algorithms to the TNM classification of malignant tumors (TNM) staging system using a dataset in which the training and testing data were from different sources. Here we compared nine data mining algorithms to the TNM staging system for colorectal survival analysis.
Methods
Two different datasets were used: 1) the National Cancer Institute's Surveillance, Epidemiology, and End Results dataset; and 2) the dataset from a single Chinese institution. An optimization and prediction system based on nine data mining algorithms as well as two variable selection methods was implemented. The TNM staging system was based on the 7th edition of the American Joint Committee on Cancer TNM staging system.
Results
When the training and testing data were from the same sources, all algorithms had slight advantages over the TNM staging system in predictive accuracy. When the data were from different sources, only four algorithms (logistic regression, general regression neural network, Bayesian networks, and Naïve Bayes) had slight advantages over the TNM staging system. Also, there was no significant differences among all the algorithms (p>0.05).
Conclusions
The TNM staging system is simple and practical at present, and data mining methods are not accurate enough to replace the TNM staging system for colorectal cancer survival prediction. Furthermore, there were no significant differences in the predictive accuracy of all the algorithms when the data were from different sources. Building a larger dataset that includes more variables may be important for furthering predictive accuracy.
doi:10.1371/journal.pone.0042015
PMCID: PMC3404978  PMID: 22848691

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