Nephrectomy improves overall survival in patients with metastatic renal cell carcinoma in cases of favorable MSKCC or ECOG prognostic features.

OBJECTIVES: The role of cytoreductive nephrectomy (CN) in the treatment of patients harboring metastatic renal cell carcinoma (mRCC) has become controversial since the emergence of effective targeted therapies. The aim of our study was to compare the overall survival (OS) between CN and non-CN groups of patients presenting with mRCC in the era of targeted drugs and to assess these outcomes among the different Memorial Sloan-Kettering Cancer Center (MSKCC) and The Eastern Cooperative Oncology Group (ECOG) performance status subgroups. METHODS AND MATERIALS: A total of 351 patients with mRCC at diagnosis recruited from 18 tertiary care centers who had been treated with systemic treatment were included in this retrospective study. OS was assessed by the Kaplan-Meier method according to the completion of a CN. The population was subsequently stratified according to MSKCC and ECOG prognostic groups. RESULTS: Median OS in the entire cohort was 37.1 months. Median OS was significantly improved for patients who underwent CN (16.4 vs. 38.1 months, P<0.001). However, subgroup analysis demonstrated that OS improvement after CN was only significant among the patients with an ECOG score of 0 to 1 (16.7 vs. 43.3 months, P = 0.03) and the group of patients with good and intermediate MSKCC score (16.8 vs. 42.4 months, P = 0.02). On the contrary, this benefit was not significant for the patients with an ECOG score of 2 to 3 (8.0 vs. 12.6 months, P = 0.8) or the group with poor MSKCC score (5.2 vs. 5.2, P = 0.9). CONCLUSIONS: CN improves OS in patients with mRCC. However, this effect does not seem to be significant for the patients in ECOG performance status groups of 2 to 3 or poor MSKCC prognostic group.

Polytetrafluoroethylene expanded prosthesis as replacement of the inferior vena cava in renal cell carcinoma with caval thrombus.

OBJECTIVE: To assess the outcomes of inferior vena cava replacement with polytetrafluoroethylene expanded prosthesis in patients with renal cell carcinoma and caval thrombosis. METHODS: All patients who underwent radical nephrectomy with inferior vena cava replacement by polytetrafluoroethylene expanded prosthesis for renal cancer associated with inferior vena cava thrombosis and a suspicion of inferior vena cava wall invasion from January 2000 to June 2011 were considered for this study. Demographic data, postoperative course, graft patency and survival data were evaluated. RESULTS: A total of 26 patients (median age 59.5 years, range 19.9-85.6 years) were included in the analysis. The median tumor diameter was 10 cm (range 5-14 cm). Histological invasion of the wall of the inferior vena cava was found in 16 (61.5%) cases. The median follow up was 28 months (range 1-136). A graft thrombosis occurred in five (19.2%) patients within the first year. Four of these patients died before the end of the second year. Patency of the inferior vena cava graft at 6 and 12 months was 88% and 79%, respectively. Overall survival probability at 3 years was 64%. CONCLUSION: Prosthetic replacement of the inferior vena cava can be carried out when invasion of the wall of the inferior vena cava is suspected. The postoperative complication rate in this subset of high-risk patients undergoing radical nephrectomy seems acceptable, and the patency of the prostheses is good in most of the cases.

National prospective study on the use of local haemostatic agents during partial nephrectomy.

OBJECTIVE: To assess the use of local haemostatic agents (HAs) in a prospective multicentre large series of partial nephrectomies (PNs). PATIENTS AND METHODS: Prospective National Observational Registry on the Practices of Haemostasis in Partial Nephrectomy (NEPHRON): the study was conducted in 54 French urological centres from 1 June to 31 December 2010. In all, 570 consecutive patients undergoing a PN were enrolled in this study in a prospective manner. The data was collected prospectively via an electronic case-report form: five different sheets were included for preoperative, perioperative, postoperative and follow-up data respectively. Information related to haemostasis was analysed. RESULTS: The median patient age was 60 years and the mean (range) tumour size was 3.68 (0.19-15) cm. An HA was primarily used in 71.4% of patients, with a statistically significant difference among surgical approaches (P = 0.024). In 91.8% of cases, a single use of a HA was sufficient for achieving haemostasis. The HA was used either alone (13.9%) or in association with sutures (80.3%). One or more additional haemostatic action(s) was needed in 12.3% of the cases. When comparing patients who received a HA with those who did not receive a HA, there was no statistical difference between the groups for tumour size (P = 0.542), collecting system drainage (P = 0.538), hospital stay (P = 0.508), operation time (P = 0.169), blood loss (P = 0.387) or transfusion rate (P = 0.713). CONCLUSION: HAs are widely used by urologists during PN. Progress is needed for standardising HA application, especially for the timing of application. For the time being, the role of the HA in nephron-sparing surgery is still to be evaluated.

Isolation and characterization of a primary proximal tubular epithelial cell model from human kidney by CD10/CD13 double labeling.

Renal proximal tubular epithelial cells play a central role in renal physiology and are among the cell types most sensitive to ischemia and xenobiotic nephrotoxicity. In order to investigate the molecular and cellular mechanisms underlying the pathophysiology of kidney injuries, a stable and well-characterized primary culture model of proximal tubular cells is required. An existing model of proximal tubular cells is hampered by the cellular heterogeneity of kidney; a method based on cell sorting for specific markers must therefore be developed. In this study, we present a primary culture model based on the mechanical and enzymatic dissociation of healthy tissue obtained from nephrectomy specimens. Renal epithelial cells were sorted using co-labeling for CD10 and CD13, two renal proximal tubular epithelial markers, by flow cytometry. Their purity, phenotypic stability and functional properties were evaluated over several passages. Our results demonstrate that CD10/CD13 double-positive cells constitute a pure, functional and stable proximal tubular epithelial cell population that displays proximal tubule markers and epithelial characteristics over the long term, whereas cells positive for either CD10 or CD13 alone appear to be heterogeneous. In conclusion, this study describes a method for establishing a robust renal proximal tubular epithelial cell model suitable for further experimentation.

Do anti-angiogenic therapies prevent brain metastases in advanced renal cell carcinoma?

BACKGROUND: We analyzed renal cell carcinoma (RCC) brain metastasis (BM) risk factors and compared BM occurrence in metastatic RCC (mRCC) treated with or without anti-angiogenic agents (AA). METHODS: Data from all consecutive metastatic RCC patients (patients) treated in a french cancer center between 1995 and 2008 were reviewed. Patients had histologically confirmed advanced RCC without synchronous BM at the time of metastasis diagnosis. AA were sorafenib, sunitinib and bevacizumab. We also included patients treated with mTor inhibitors, temsirolimus and everolimus, as they also demonstrated anti-angiogenic activities. Characteristics of the two groups treated with or without AA were compared with a Fisher exact test. Impact of AA on overall survival (OS) and cumulative rate of brain metastasis (CRBM) was explored by Kaplan-Meier method. RESULTS: One hundred and ninety-nine patients with advanced RCC were identified, 51 treated with AA and 148 without AA. The median follow-up duration was 40 months. BM occurred in 35 patients. Characteristics between AA treated and non-AA treated groups were unbalanced and favoring better prognostic factors in AA treated group. Median OS was 24 months. AA treatment was not associated with a lower CRBM (HR = 0.58 [0.26-1.30], P = 0.187). Median survival free of BM was 11.8 months, CI95% (4.95-18.65) in the group without AA treatment and 28.9 months in the AA group, CI95% (18.64-39.16). Alkaline phosphatase (AP) was an independent prognostic factor for BM (P = 0.05). In multivariate Cox model, after adjustment to AP, AA did not improve the CRBM (aHR = 0.53 [0.22-1.32]). CONCLUSION: In this retrospective study, AA did not decrease significantly the CRBM. Elevated AP was a predictive factor for BM in mRCC.

Contemporary management of adrenocortical carcinoma.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare and typically aggressive malignancy. Available recommendations are based primarily on retrospective series or expert opinions, and only few prospective clinical studies have yet been published. OBJECTIVE: To combine the available evidence for diagnostic work-up and treatment of ACC to a contemporary recommendation on the management of this disease. EVIDENCE ACQUISITION: We conducted a systematic literature search for studies conducted on humans and published in English using the Medline/PubMed database up to 31 January 2011. In addition, we screened published abstracts at meetings and several Web sites for recommendations on ACC management. EVIDENCE SYNTHESIS: In patients with suspected localised ACC, a thorough endocrine and imaging work-up is followed by complete (R0) resection of the tumour by an expert surgeon. In experienced hands, laparoscopic adrenalectomy is probably as effective and safe for localised and noninvasive ACC as open surgery. Most clinicians agree that mitotane should be used as adjuvant therapy in the majority of patients, as they have a high risk for recurrence. An international panel has suggested using tumour stage, resection status, and the proliferation marker Ki67 as guidance for or against adjuvant therapy. In patients with advanced disease at presentation or recurrence not amenable to complete resection, a surgical approach is frequently inadequate. In these cases, mitotane alone or in combination with cytotoxic drugs is the treatment of choice. The most promising regimens (etoposide, doxorubicin, cisplatin plus mitotane, and streptozotocin plus mitotane) are currently compared in an international phase 3 trial, and results should be available by the end of 2011. Several targeted therapies are under investigation and may lead to new treatment options. Management of endocrine manifestations with steroidogenesis inhibitors is required in patients suffering uncontrolled hormone excess. CONCLUSIONS: Detailed recommendations are provided to guide the management of patients with ACC.

Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE: Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS: Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION: All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS: Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS: RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.

[Management of side effects of targeted therapies in renal cancer: nephrological side effects]. / Gestion des effets secondaires des thérapies ciblées dans le cancer du rein : effets secondaires néphrologiques.

Several types of nephrological side-effects can occur during treatment with targeted therapy: high blood pressure, proteinuria, thrombotic microangiopathy, kidney failure, etc. Screening and treatment for high blood pressure, proteinuria and kidney failure are recommended during treatment with molecular targeted therapy (mainly for anti-VEGF). If BP is greater than 140/90mmHg on two measurements, it must be treated before the start of treatment. Self-measurement or ambulatory measurement of blood pressure is recommended. All antihypertensive drugs may be used apart from those, which interfere with cytochrome P450 (verapamil and diltiazem). Specialist advice (cardiology or nephrology) is recommended in the event of uncontroled hypertension. It is essential to monitor proteinuria with a urine strip test: if proteinuria is less than 2+ (grade 1), maintain treatment with molecular targeted therapy; if proteinuria is greater or equal to 2+ (grade2 or 3, confirmed by weight assay), specialist advice is required. Persisting proteinuria of grade2 or 3 requires nephrological monitoring. Thrombotic microangiopathy must be investigated in the event of hypertension greater than grade2 and/or proteinuria greater than 2+.

Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma.

AIMS: In kidney cancer, new anti-angiogenic therapies have emerged requiring parameters of effectiveness. The aim was to analyse the expression of endocan or endothelial cell-specific molecule-1, which is a proteoglycan up-regulated in presence of pro-angiogenic factors. METHOD AND RESULTS: We investigated 44 renal clear cell carcinomas (RCC) and 25 papillary carcinomas (PC). Circulating endocan was detected by enzyme-linked immunosorbent assays (ELISA) in 14 patients with RCC, in eight with PC and in 15 healthy volunteers. Endocan was detected by immunohistochemistry in endothelial cells in almost all the cases of RCC without immunoreactivity in tumour cells. In PC, only 5/25 tumours exhibited weak immunoreactivity. Reverse transcriptase-polymerase chain reaction study confirmed that endocan levels were strongly increased in RCC. Endocan was also detected by ELISA at levels from 3- to 10-fold higher in the sera of patients with RCC. In vitro, addition of sunitinib prevented the release of endocan in human umbilical vascular endothelial cells when induced by vascular endothelial growth factor. CONCLUSIONS: Our results showed that endocan is overexpressed in patients with RCC. Endocan could therefore appear as a marker of interest in the follow-up and may be a potential parameter to monitor the tumour response to anti-angiogenic therapeutics.

Limited prognostic value of tumor necrosis in patients with renal cell carcinoma.

OBJECTIVES: To test whether tumor necrosis (TN) could improve the prognostic ability of the predictors of 2 established prognostic renal cell carcinoma (RCC) models. Presence of TN within the nephrectomy specimen is considered an important prognostic marker in patients with RCC. However, its added prognostic value along with established cancer-specific mortality (CSM) predictors has never been formally tested. METHODS: We retrospectively analyzed data of 1526 patients with all stages of RCC, who were treated with radical or partial nephrectomy at 6 institutions between 1988 and 2004. Univariate and multivariate Cox-regression models tested the statistical significance of TN in CSM predictions. Covariates consisted of TNM stage, Fuhrman grade, tumor size, and symptom classification. The analyses first addressed the entire patient population (n=1526) and then repeated in patients with exclusive clear-cell histology (n=1320). RESULTS: TN was present in 476 patients (31.2%). TN was a statistically significant predictor of CSM (hazard ratio: 2.73; P<.001) but not an independent predictor of CSM (adjusted hazard ratio: 0.88; P=.4). Accuracy of TN ranked sixth among 7 examined predictors and TN failed to improve the accuracy of other variables. The same results were recorded in patients with exclusive clear-cell histology. CONCLUSIONS: TN does not improve the accuracy of established predictors of CSM that are used in 2 prognostic RCC models for patients with RCC of all stages.

Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery.

BACKGROUND: The occurrence of positive surgical margins (PSMs) after partial nephrectomy (PN) is rare, and little is known about their natural history. OBJECTIVE: To identify predictive factors of cancer recurrence and related death in patients having a PSM following PN. DESIGN, SETTING, AND PARTICIPANTS: Some 111 patients with a PSM were identified from a multicentre retrospective survey and were compared with 664 negative surgical margin (NSM) patients. A second cohort of NSM patients was created by matching NSM to PSM for indication, tumour size, and tumour grade. MEASUREMENTS: PSM and NSM patients were compared using student t tests and chi-square tests on independent samples. A Cox proportional hazards regression model was used to test the independent effects of clinical and pathologic variables on survival. RESULTS AND LIMITATIONS: Mean age at diagnosis was 61+/-12.5 yr. Mean tumour size was 3.5+/-2 cm. Imperative indications accounted for 39% (43 of 111) of the cases. Some 18 patients (16%) underwent a second surgery (partial or total nephrectomy). With a mean follow-up of 37 mo, 11 patients (10%) had recurrences and 12 patients (11%) died, including 6 patients (5.4%) who died of cancer progression. Some 91% (10 of 11) of the patients who had recurrences and 83% of the patients (10 of 12) who died belonged to the group with imperative surgical indications. Rates of recurrence-free survival, of cancer-specific survival, and of overall survival were the same among NSM patients and PSM patients. The multivariable Cox model showed that the two variables that could predict recurrence were the indication (p=0.017) and tumour location (p=0.02). No other variable, including PSM status, had any effect on recurrence. None of the studied parameters had any effect on the rate of cancer-specific survival. CONCLUSIONS: PSM status occurs more frequently in cases in which surgery is imperative and is associated with an increased risk of recurrence, but PSM status does not appear to influence cancer-specific survival. Additional follow-up is needed.

Conditional survival predictions after nephrectomy for renal cell carcinoma.

PURPOSE: Conditional survival implies that on average long-term cancer survivors have a better prognosis than do newly diagnosed individuals. We explored the effect of conditional survival in renal cell carcinoma. MATERIALS AND METHODS: We studied 3,560 patients with renal cell carcinoma of all stages treated with nephrectomy. We applied conditional survival methodology to a previously reported posttreatment nomogram predicting survival after nephrectomy for patients with renal cell carcinoma stage I to IV. We used the same predictor variables that were integrated in the original multivariable Cox regression models, namely TNM stage, Fuhrman grade, tumor size and symptom classification. To validate the conditional survival nomogram we used an independent cohort of 3,560 patients from 15 institutions. RESULTS: The 5-year survival of patients immediately after nephrectomy was 74.2%, which increased to 80.4%, 85.1%, 90.6% and 89.6% at 1, 2, 5 and 10 years after nephrectomy, respectively. The predicted probabilities varied by as much as 50% when, for example, predictions of renal cell carcinoma specific mortality at 10 years were made after nephrectomy vs 5 years later. Within the external validation cohort the accuracy of the conditional nomogram was 89.5%, 90.5%, 88.5% and 86.7% at 1, 2, 5 and 10 years after nephrectomy. CONCLUSIONS: We developed (2,530) and externally validated (3,560) a conditional nomogram for predicting renal cell carcinoma specific mortality that allows consideration of the length of survivorship. Our tool provides the most realistic prognosis estimates with high accuracy.

Survival of patients with nonmetastatic pT3 renal tumours: a matched comparison of laparoscopic vs open radical nephrectomy.

OBJECTIVES: To compare the oncological outcome of patients with pT3 renal tumours treated either by laparoscopic radical nephrectomy (LRN) or open RN (ORN). PATIENTS AND METHODS: In a retrospective review of a multi-institutional database, we identified 1003 patients with a T3N0M0 renal tumour and with no vena caval invasion. Sixty-five patients treated by LRN were matched with up to four patients treated by ORN. Exact matches were made for age, gender, tumour size, perirenal fat invasion, renal vein invasion, and histological subtype. Following the matching process there were 44 patients treated by LRN and 135 by ORN. Qualitative and continuous variables were compared using chi-square and independent-sample t-tests, respectively. Differences in survival were compared using the Kaplan-Meier method. A Cox regression model was used to test the effect of variables on survival. RESULTS: The two groups were comparable for age (P = 0.4), gender, tumour size (P = 0.4), tumour grade (P = 0.25) and histological subtype (P = 0.45). The mean follow-up was longer in the ORN group (55 vs 28 months, P < 0.001). There was no difference in survival between the ORN and LRN groups in the whole T3 population (P = 0.7), in those with perirenal fat invasion (P = 0.9), or in the subset with renal vein invasion (P = 0.31). In univariate analysis, the only predictor for death from cancer was tumour grade (P = 0.05). In multivariate analysis, no variable was significantly associated with cancer survival. CONCLUSIONS: LRN has no adverse effect on cancer survival compared to ORN in patients with microscopic T3 renal cancer. Additional prospective evaluation is warranted.

Partial cystectomy does not undermine cancer control in appropriately selected patients with urothelial carcinoma of the bladder: a population-based matched analysist.

OBJECTIVES: Cancer control outcomes after partial cystectomy (PC) are not well studied. We compared the population-based rates of overall (OS) and cause-specific survival (CSS) in patients with urothelial carcinoma of the urinary bladder (UCB) treated with PC or radical cystectomy (RC). METHODS: Within the Surveillance Epidemiology and End Results-9 database, we identified 7243 patients treated with PC (n = 1573) or RC (n = 5670), who had pathologic T(1-4)N(1-2)M(0) UCB. Matched Kaplan-Meier survival analyses compared the effect of PC vs RC on OS and CSS. RESULTS: In the entire cohort, the OS and CSS estimates at 5 years were 57.2% and 76.4%, respectively, for PC patients and 50.2% and 65.8%, respectively, for RC patients (P < .001). In the cohort matched for age, race, pT stage, pN stage, tumor grade, and year of surgery, at 5 years the OS and CSS estimates were 56.0% and 73.5%, respectively, for PC patients, and 50.9% and 67.5%, respectively, for RC patients (OS, P = .03 and CSS, P < .001). When the number of removed lymph nodes was added to the matching criteria, the 5-year OS and CSS estimates were 57.2% and 70.3%, respectively, for PC patients, and 54.6% and 69.2%, respectively, for RC patients (HR 1.1, P = .3 and HR 1.1, P = .5). CONCLUSIONS: Partial cystectomy does not undermine cancer control in appropriately selected patients with UCB.

Thirty-day mortality after transurethral resection of the prostate in patients treated with androgen deprivation therapy.

BACKGROUND AND PURPOSE: Seven percent of patients with prostate cancer (PCa) who are exposed to androgen deprivation therapy (ADT) may need transurethral resection of the prostate (TURP). Our objective was to examine the rate and the predictors of 30-day mortality (30dM) after TURP in patients who were exposed to ADT in a large, contemporary Canadian cohort. PATIENTS AND METHODS: We assessed the 30dM rate after TURP in 853 men with the diagnosis of PCa who were treated with primary ADT or radiation therapy followed by ADT. The effect of age, comorbidity (coded according to the Charlson Comorbidity Index [CCI]), number of previous TURP procedures, history of radiation therapy, exposure to antiandrogens, and the type and the duration of ADT before TURP were all tested in univariable and multivariable logistic regression models that predicted 30dM after TURP. RESULTS: During the initial 30 days after TURP, 38 deaths occurred (4.5%, 95% confidence interval: 3.2%-6.2%). Of all variables, the CCI was the only statistically significant (P = 0.001) predictor of 30dM after TURP. The accuracy of CCI in predicting 30dM after TURP in individual patients was 65.1%. Lack of consideration of clinical variables that could predict the 30dM rate after TURP, such as prostate size or prostate-specific antigen level, represents a limitation of this study. CONCLUSIONS: A substantial risk of 30dM is associated with TURP that is performed in patients who are exposed to ADT. Unfortunately, the predictors used in this analysis could not define the individual risk of 30dM with sufficient accuracy. Nonetheless, the average 4.5% risk should be considered at the time of informed consent.

External validation of a nomogram predicting mortality in patients with adrenocortical carcinoma.

OBJECTIVE: To develop nomograms predicting cancer-specific and all-cause mortality in patients managed with either surgery or no surgery for adrenocortical carcinoma (ACC). PATIENTS AND METHODS: The models were developed in 205 patients with ACC and externally validated using 207 other patients with ACC, identified in the 1973-2004 Surveillance, Epidemiology and End Results database. The predictors comprised age, gender, race, stage and surgery status. Nomograms based on Cox regression model-derived coefficients were used for predicting the cancer-specific and all-cause mortality, and were tested using area under the receiver operating characteristics (ROC) curve. RESULTS: In cancer-specific analyses, the median survival of patients within the development cohort was 26 months, vs 71 months in the external validation cohort (P < 0.001). In overall survival analyses, the median values were 21 vs 32 months for, respectively, the development and the external validation cohort (P < 0.001). Three variables (age, stage and surgical status) were included in the nomograms predicting cancer-specific and all-cause mortality. In the external validation cohort, the nomograms achieved between 72 and 80% accuracy for prediction of cancer-specific or all-cause mortality at 1-5 years after either surgery or diagnosis of ACC for non-surgical patients. CONCLUSION: Our models are the first standardized and individualized prognostic tools for patients with ACC. Their accuracy was confirmed within a large external population-based cohort of patients with ACC.

Baseline renal function, ischaemia time and blood loss predict the rate of renal failure after partial nephrectomy.

OBJECTIVE: To identify independent predictors of renal failure after partial nephrectomy (PN) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Data were available for 166 patients with pathological T1-3 N0M0 RCC treated with PN. Renal failure after PN was defined as a decrease in glomerular filtration rate (GFR) of >25% (RIFLE criteria). The GFR before and after PN was estimated using the Modification of Diet in Renal Disease study group equation. Univariable and multivariable logistic regression models were used to assess a decrease of >25% in GFR from the preoperative level. Candidate predictor variables were age, gender, PN indication (absolute vs relative), preoperative GFR, tumour size, perioperative blood loss, surgery duration and clamping time. RESULTS: After PN, 22 (13.3%) patients had a decrease in GFR of >25%. The perioperative blood loss (P = 0.02), clamping time (P = 0.04) and preoperative GFR (P = 0.002) were independent predictors of a decrease in GFR of >25%. CONCLUSIONS: We identified two important potentially modifiable variables that should be considered in the planning of PN, i.e. the clamping time and blood loss. It is possible that selective referral to experienced surgeons who can perform PN within short surgical and clamping times, and with minimal blood loss, could minimize the rate of renal failure, especially in patients with an underlying renal function impairment.

Development and external validation of a highly accurate nomogram for the prediction of perioperative mortality after transurethral resection of the prostate for benign prostatic hyperplasia.

PURPOSE: Benign prostatic hyperplasia affects 60% of men at the age of 60 years. Transurethral resection of the prostate is the gold standard of therapy. We assessed the 30-day mortality rate after transurethral resection of the prostate for benign prostatic hyperplasia, identified risk factors related to 30-day mortality and developed a model that discriminates among individual 30-day mortality risk levels. MATERIALS AND METHODS: We performed development (7,362) and external validation (7,362) of a multivariable logistic regression model predicting the individual probability of 30-day mortality after transurethral resection of the prostate based on an administrative data set (Quebec Health Plan) of 14,724 patients 43 to 99 years old treated between January 1, 1989 and December 31, 2000. RESULTS: Overall 30-day mortality occurred in 58 patients (0.4%) undergoing transurethral resection of the prostate. On univariable analyses increasing age (p <0.001) and increasing Charlson comorbidity index (p <0.001) were statistically significant predictors of 30-day mortality after transurethral resection of the prostate. Conversely annual surgical volume was not. On multivariable analyses age (p <0.001) and Charlson comorbidity index (p <0.001) reached independent predictor status. The accuracy of the age and Charlson comorbidity index based nomogram that predicts the individual probability of 30-day mortality after transurethral resection of the prostate was 83% in the external validation cohort. CONCLUSIONS: Age and Charlson comorbidity index are important determinants of 30-day mortality after transurethral resection of the prostate. The combination of these parameters allows an 83% accurate prediction of individual 30-day mortality risk after transurethral resection of the prostate. Despite limitations such as the need for additional external validations and possibly the need for inclusion of clinical parameters, the use of the current model is warranted for the purpose of informed consent before transurethral resection of the prostate and/or for patient counseling.

A population based assessment of perioperative mortality after cystectomy for bladder cancer.

PURPOSE: Large variability exists in the rates of perioperative mortality after cystectomy. Contemporary estimates range from 0.7% to 5.6%. We tested several predictors of perioperative mortality and devised a model for individual perioperative mortality prediction. MATERIALS AND METHODS: We relied on life tables to quantify 30, 60 and 90-day mortality rates according to age, gender, stage (localized vs regional), grade, type of surgery (partial vs radical cystectomy), year of cystectomy and histological bladder cancer subtype. We fitted univariable and multivariable logistic regression models using 5,510 patients diagnosed with bladder cancer and treated with partial or radical cystectomy within 4 SEER (Surveillance, Epidemiology, and End Results) registries between 1984 and 2004. We then externally validated the model on 5,471 similar patients from 5 other SEER registries. RESULTS: At 30, 60 and 90 days the perioperative mortality rates were 1.1%, 2.4% and 3.9%, respectively. Age, stage and histological subtype represented statistically significant and independent predictors of 90-day mortality. The combined use of these 3 variables and of tumor grade resulted in the most accurate model (70.1%) for prediction of individual probability of 90-day mortality after cystectomy. CONCLUSIONS: The accuracy of our model could potentially be improved with the consideration of additional parameters such as surgical and hospital volume or comorbidity. While better models are being developed and tested we suggest the use of the current model in individual decision making and in informed consent considerations because it provides accurate predictions in 7 of 10 patients.

Nephrectomy improves survival in patients with invasion of adjacent viscera and absence of nodal metastases (stage T4N0 renal cell carcinoma).

OBJECTIVE: To examine the cancer-specific mortality (CSM) of patients with T4N0-2M0 renal cell carcinoma (RCC) treated with either nephrectomy (RN) or no surgery (NS). PATIENTS AND METHODS: Of 43 143 patients with RCC identified in the Surveillance, Epidemiology and End Results database, 310 had tumours involving adjacent organs with no evidence of distant metastases (T4NanyM0) and had RN (246, 79.4%) or NS (64, 20.6%). Kaplan-Meier analyses, Cox regression and competing-risks regression models were used to compare the effect of RN vs NS on CSS. RESULTS: In patients with T4N0 disease the median survival benefit associated with RN vs NS was 42 months (48 vs 6 months, P < 0.001). Conversely, the median survival in patients T4N1-2 was no different between RN and NS (9.3 vs 9.1 months, P = 0.9). Multivariable analyses in T4N0 cases indicated a substantial survival disadvantage for patients having NS vs RN (hazard ratio 4.8, P < 0.001). Conversely, in patients with N1-2 stages, the CSS was virtually the same for NS and RN (hazard ratio 0.9, P = 0.9). Competing-risks regression models confirmed the benefit of RC in patients with T4N0 and the lack of benefit in those with T4N1-2 disease, after controlling for other-cause mortality. CONCLUSION: Our data suggest a survival benefit in patients with T4N0 RCC treated with RC. By contrast, RN seems to have no effect on survival in patients with evidence of nodal metastases.