Age-adjusted incidence, mortality, and survival rates of stage-specific renal cell carcinoma in North America: a trend analysis

Background

The rising incidence of renal cell carcinoma (RCC) has been largely attributed to the increasing use of imaging procedures.

Objective

Our aim was to examine stage-specific incidence, mortality, and survival trends of RCC in North America.

Design, setting, and participants

We computed age-adjusted incidence, survival, and mortality rates using the Surveillance Epidemiology and End Results database. Between 1988 and 2006, 43 807 patients with histologically confirmed RCC were included.

Measurements

We calculated incidence, mortality, and 5-yr survival rates by year. Reported findings were stratified according to disease stage.

Results and limitations

Age-adjusted incidence rate of RCC rose from 7.6 per 100 000 person-years in 1988 to 11.7 in 2006 (estimated annual percentage change [EAPC]: +2.39%; p < 0.001). Stage-specific age-adjusted incidence rates increased for localized stage: 3.8 in 1988 to 8.2 in 2006 (EAPC: +4.29%; p < 0.001) and decreased during the same period for distant stage: 2.1 to 1.6 (EAPC: −0.57%; p = 0.01). Stage-specific survival rates improved over time for localized stage but remained stable for regional and distant stages. Mortality rates varied significantly over the study period among localized stage, 1.3 in 1988 to 2.4 in 2006 (EAPC: +3.16%; p < 0.001), and distant stage, 1.8 in 1988 to 1.6 in 2006 (EAPC: −0.53%; p = 0.045). Better detailed staging information represents a main limitation of the study.

Conclusions

The incidence rates of localized RCC increased rapidly, whereas those of distant RCC declined. Mortality rates significantly increased for localized stage and decreased for distant stage. Innovation in diagnosis and management of RCC remains necessary.     

A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma

Background

Nephron-sparing surgery (NSS) can safely be performed with slightly higher complication rates than radical nephrectomy (RN), but proof of oncologic effectiveness is lacking.

Objective

To compare overall survival (OS) and time to progression.

Design, setting, and participants

From March 1992 to January 2003, when the study was prematurely closed because of poor accrual, 541 patients with small (≤5 cm), solitary, T1–T2 N0 M0 (Union Internationale Contre le Cancer [UICC] 1978) tumours suspicious for renal cell carcinoma (RCC) and a normal contralateral kidney were randomised to NSS or RN in European Organisation for Research and Treatment of Cancer Genito-Urinary Group (EORTC-GU) noninferiority phase 3 trial 30904.

Intervention

Patients were randomised to NSS (n = 268) or RN (n = 273) together with limited lymph node dissection (LND).

Measurements

Time to event end points was compared with log-rank test results.

Results and limitations

Median follow-up was 9.3 yr. The intention-to-treat (ITT) analysis showed 10-yr OS rates of 81.1% for RN and 75.7% for NSS. With a hazard ratio (HR) of 1.50 (95% confidence interval [CI], 1.03–2.16), the test for noninferiority is not significant (p = 0.77), and test for superiority is significant (p = 0.03). In RCC patients and clinically and pathologically eligible patients, the difference is less pronounced (HR = 1.43 and HR = 1.34, respectively), and the superiority test is no longer significant (p = 0.07 and p = 0.17, respectively). Only 12 of 117 deaths were the result of renal cancer (four RN and eight NSS). Twenty-one patients progressed (9 after RN and 12 after NSS). Quality of life and renal function outcomes have not been addressed.

Conclusions

Both methods provide excellent oncologic results. In the ITT population, NSS seems to be significantly less effective than RN in terms of OS. However, in the targeted population of RCC patients, the trend in favour of RN is no longer significant. The small number of progressions and deaths from renal cancer cannot explain any possible OS differences between treatment types.     

Growth kinetics of renal masses: analysis of a prospective cohort of patients undergoing active surveillance

Background

Active surveillance (AS) represents a treatment option for renal masses in patients who are not surgical candidates either because of existing comorbidities or patient choice. Among renal masses undergoing AS, some grow rapidly and require treatment or progress to metastatic disease. Patient and tumour characteristics related to this more aggressive behaviour have been poorly studied.

Objective

To report the analysis of a multi-institutional cohort of patients undergoing AS for small renal masses.

Design, setting, and participants

This prospective study included 82 patients with 84 renal masses who underwent AS in three Canadian institutions between July 2001 and June 2009.

Intervention

All patients underwent AS for renal masses presumed to be renal cell carcinoma (RCC) as based on diagnostic imaging.

Measurements

Age, sex, symptoms at presentation, maximum diameter at diagnosis (cm), tumour location (central/peripheral), degree of endophytic component (1–100%), and tumour consistency (solid/cystic) were used to develop a predictive model of the tumour growth rate using binary recursive partitioning analysis with a repeated measures outcome.

Results and limitations

With a median follow-up of 36 mo (range: 6–96), the mean annual renal mass growth rate for the entire cohort was 0.25 cm/yr (standard deviation [SD]: 0.49 cm/yr). Only one patient (1.2%) developed metastatic RCC. Amongst all variables, maximum diameter at diagnosis was the only predictor of tumour growth rate, and two distinct growth rates were identified. Masses that are ≥2.45 cm in largest diameter at diagnosis grow faster than smaller masses. This series was limited by its moderate sample size, although it is the largest published prospective series to date.

Conclusions

We confirm that most renal masses grow slowly and carry a low metastatic potential. Tumour size is a predictor of tumour growth rate, with renal masses <2.45 cm growing more slowly than masses >2.45 cm.     

Radiofrequency ablation versus partial nephrectomy in patients with solitary clinical T1a renal cell carcinoma: comparable oncologic outcomes at a minimum of 5 years of follow-up

Background

Long-term comparative outcomes for radiofrequency ablation (RFA) versus partial nephrectomy (PN) for the primary treatment of clinical T1a renal cell carcinoma (RCC) have not previously been reported.

Objective

Report comparative 5-yr oncologic outcomes for RFA versus PN in patients with clinical T1a RCC.

Design, setting, and participants

Observational single-institution cohort study, involving consecutive patients with a solitary histologically confirmed T1a RCC treated by RFA or PN and followed for a minimum of 5 yr. Those presenting with synchronous multiple, metachronous, bilateral, and/or metastatic disease, a history of hereditary RCC syndromes, a family history of RCC, and with post-treatment follow-up <5 yr were excluded from analysis.

Measurements

The Kaplan-Meier method was used to determine 5-yr overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (local RFS), overall disease-free survival (DFS), and metastasis-free survival (MFS) for RFA versus PN. Survival curves were compared using the log-rank test. A p value ≤0.05 was considered statistically significant.

Results and limitations

A total of 37 patients in each group met the selection criteria. The RFA cohort was significantly older and had more advanced comorbidities, but other patient characteristics were similar. For RFA versus PN, median follow-up was 6.5 yr (interquartile range [IQR]: 5.8–7.1) versus 6.1 yr (IQR: 5.4–7.3) (p = 0.68), respectively. The 5-yr OS was 97.2% versus 100% (p = 0.31), CSS was 97.2% versus 100% (p = 0.31), DFS was 89.2% versus 89.2% (p = 0.78), local RFS was 91.7% versus 94.6% (p = 0.96), and MFS was 97.2% versus 91.8% (p = 0.35), respectively. Study limitations are retrospective data analysis, loss to follow-up, limited statistical power, and limited generalizability of our data.

Conclusions

In appropriately selected patients, RFA is an effective minimally invasive therapy for the treatment of cT1a RCC, yielding comparable long-term oncologic outcomes to nephron-sparing surgery.     

Preoperative nutritional status is an important predictor of survival in patients undergoing surgery for renal cell carcinoma

Background

The role of malnutrition has not been well studied in patients undergoing surgery for renal cell carcinoma (RCC).

Objective

Our aim was to evaluate whether nutritional deficiency (ND) is an important determinant of survival following surgery for RCC.

Design, setting, and participants

A total of 369 consecutive patients underwent surgery for locoregional RCC from 2003 to 2008. ND was defined as meeting one of the following criteria: body mass index <18.5 kg/m², albumin <3.5 g/dl, or preoperative weight loss ≥5% of body weight.

Intervention

All patients underwent radical or partial nephrectomy.

Measurements

Primary outcomes were overall and disease-specific mortality. Covariates included age, Charlson comorbidity index (CCI), preoperative anemia, tumor stage, Fuhrman grade, and lymph node status. Multivariate analysis was performed using a Cox proportional hazards model. Mortality rates were estimated using the Kaplan-Meier product-limit method.

Results and limitations

Eighty-five patients (23%) were categorized as ND. Three-year overall and disease-specific survival were 58.5% and 80.4% in the ND cohort compared with 85.4% and 94.7% in controls, respectively (p < 0.001). ND remained a significant predictor of overall mortality (hazard ratio [HR]: 2.41, 95% confidence interval [CI], 1.40–4.18) and disease-specific mortality (HR: 2.76; 95% CI, 1.17–6.50) after correcting for age, CCI, preoperative anemia, stage, grade, and nodal status. This study is limited by its retrospective nature.

Conclusions

ND is associated with higher mortality in patients undergoing surgery for locoregional RCC, independent of key clinical and pathologic factors. Given this mortality risk, it may be important to address nutritional status preoperatively and counsel patients appropriately.     

Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma

Background

Animal models are instrumental in understanding disease pathophysiology and mechanisms of therapy action and resistance in vivo.

Objective

To establish and characterize a panel of mouse models of renal cell carcinoma (RCC) derived from patients undergoing radical nephrectomy.

Design, setting, and participants

In vivo and in vitro animal experiments.

Measurements

Tumor tissues obtained during surgery were implanted into the subcutaneous space of female BALB/c nude mice and serially passaged into new mice. Tumors were characterized by histology, short tandem repeat (STR) fingerprinting, von Hippel-Lindau (VHL) gene sequencing, and single nucleotide polymorphism (SNP) analysis. Tumor-bearing mice were treated with sunitinib or everolimus. Primary cell cultures were derived from patient tumors and transfected with a lentivirus carrying the luciferase gene. Four subcutaneous xenograft mouse models were developed, representing papillary type 1, papillary type 2, clear cell, and clear cell with sarcomatoid features RCC.

Results and limitations

RCC mouse models were established from four patients with distinct histologies of RCC. Tumor growth was dependent on histologic type, the size of the implanted tumor chip, and the passage number. Mouse tumors accurately represented their respective original patient tumors, as STR fingerprints were matching, histology was comparable, and SNP profiles and VHL mutation status were conserved with multiple passages. Bioluminescence imaging results were commensurate with subcutaneous xenograft growth patterns. Mice treated with sunitinib and everolimus exhibited an initial response, followed by a later stage of resistance to these agents, which mimics the clinical observations in patients with RCC.

Conclusions

We developed four mouse xenograft models of RCC with clear-cell and papillary histologies, with stable histologic and molecular characteristics. These models can be used to understand the basic biology of RCC as well as response and resistance to therapy.     

Prognostic Value of Capsular Invasion for Localized Clear-Cell Renal Cell Carcinoma

Background

The impact of capsular invasion on the survival of patients undergoing surgery for renal cell carcinoma (RCC) has attracted little attention in the literature and remains controversial.

Objectives

To evaluate the value of capsular invasion, without perirenal fat invasion, on the prognosis of patients with localized clear-cell RCC.

Design, setting, and participants

Between 1984 and 2007, we retrospectively reviewed the records of 317 consecutive patients with localized clear-cell RCC (pT1–T2N0M0) who underwent radical nephrectomy or nephron-sparing surgery at our institution. Overall, 299 patients were eligible for the study. We analyzed clinical (presentation and body mass index [BMI]) and pathologic (tumor size, Fuhrman nuclear grade, collecting system invasion, microvascular invasion, and capsular involvement) parameters.

Measurements

Recurrence-free survival (RFS) and cancer-specific survival (CSS) were investigated using the Kaplan-Meier method, and the Cox regression model was used to determine the significant prognostic factors based on multivariate analysis.

Results and limitations

Renal capsular invasion was observed in 106 of 299 patients (35.5%). Capsular invasion had a statistically significant association with age, symptomatic presentation, tumor diameter, pathologic stage, collecting system invasion, and microvascular invasion. The mean follow-up was 60.5 mo (range: 1–249). The 5-yr RFS and CSS rates for tumors with capsular invasion were significantly lower compared with rates for tumors without invasion (77.7% vs 92.3% and 85.5% vs 95.7%, respectively; p = 0.0004). Multivariate analysis showed that BMI (hazard ratio [HR] = 0.19), stage (HR = 2.45), and capsular invasion (HR = 3.36) were independent prognostic factors of disease recurrence. With respect to CSS, BMI (HR = 0.20), tumor size (HR = 1.13), and capsular invasion (HR = 4.03) were the factors related to death. Nevertheless, we recognize that these findings may be limited by the study's retrospective, single-institution design.

Conclusions

Our findings suggest that capsular invasion is associated with poor survival in patients with localized clear-cell RCC.     

Chronic kidney disease after nephrectomy in patients with small renal masses: a retrospective observational analysis

Context

Chronic kidney disease (CKD) is a worldwide health threat associated with increased cardiovascular disease and mortality.

Objective

To examine postoperative CKD in patients with small renal masses (SRMs) treated with partial nephrectomy (PN) or radical nephrectomy (RN).

Design, setting, and participants

A US National Cancer Institute Surveillance Epidemiology and End Results (SEER)–Medicare-linked retrospective cohort of 4633 T1aN0M0 renal cell carcinoma (RCC) patients who underwent PN or RN.

Outcome measurements and statistical analysis

The primary outcome of interest was the onset of CKD stage ≥3. Secondary end points comprised acute renal failure (ARF), chronic renal insufficiency (CRI), anemia in CKD, and end-stage renal disease (ESRD). Kaplan-Meier and Cox regression analyses were performed.

Results and limitations

Postpropensity matching resulted in 840 RN and PN patients. In multivariable analyses, RN patients were 1.9-, 1.4-, 1.8-, and 1.8-fold more likely to have an occurrence of CKD, ARF, CRI, and anemia in CKD, respectively (all p ≤ 0.004). The risk of ESRD between treatment groups failed to achieve statistical significance (p = 0.06).

Conclusions

PN is associated with more favorable postoperative renal function outcomes relative to RN in the setting of SRMs.     

Is There a Need to Further Subclassify pT2 Renal Cell Cancers as Implemented by the Revised 7th TNM Version?

Background

The recently modified TNM classification of renal cell carcinoma (RCC) (7th edition) has implemented a subdivision of pT2 tumours into stage pT2a (>7 or ≤10 cm) versus pT2b disease (>10 cm).

Objective

Our aim was to evaluate whether this subdivision of pT2 RCC is justified due to a clinical prognosis divergence between the two groups (pT2a vs pT2b)

Design, setting, and participants

In total, 5122 patients were subjected to either radical nephrectomy or nephron-sparing surgery at three centres in Germany (University Hospitals of Hannover, Homburg/Saar, and Marburg). Patients were reclassified into stage pT2a and pT2b according to the maximum tumour diameter as suggested by the 7th revised version of the TNM classification system.

Measurements

The t test and Fisher exact test were applied to evaluate the comparability of the two groups (pT2a vs pT2b) regarding several additional patients’ and tumour-specific characteristics of known prognostic relevance for RCC. Univariable (Kaplan-Meier analysis) and multivariable statistical analyses (Cox proportional hazards regression model) were applied to identify a possible difference between the two groups (pT2a vs pT2b) regarding cancer-specific survival (CSS).

Results and limitations

Applying the new TNM classification, 579 previously pT2-staged patients were divided into 445 (76.9%) with pT2a and 134 (23.1%) with pT2b tumours. Kaplan-Meier curves revealed no significant difference in CSS between pT2a and pT2b patients; 5-yr CSS was 79.0% and 74.1%, respectively (p = 0.38). When applying multivariable analysis, unlike tumour grade and N/M status, pT2 subclassification failed to independently predict survival in RCC patients.

Conclusions

The new subclassification of pT2 RCC into two different subgroups as suggested by the latest modification of the TNM system does not yield additional/prognostic information.     

Observation Should be Considered as an Alternative in Management of Renal Masses in Older and Comorbid Patients

Background

Renal masses diagnosed in older and comorbid patients represent a challenge with regard to treatment.

Objective

To evaluate clinical outcome and tumor progression in patients with renal masses managed by observation due to age and comorbidity.

Design, setting, and participants

The medical records of 63 consecutive patients with renal masses primarily managed by observation during 2002–2007 were reviewed retrospectively and analyzed. The mean age for all patients at diagnosis was 76.6 yr, and 59% were male. Mean tumor size was 4.3 cm in diameter at diagnosis. Of these, 30% had Eastern Cooperative Oncology Group performance status (PS) of 2 or 3, 78% were American Society of Anesthesiologists (ASA) class 3, and the patients had a mean of 2.8 other medical conditions.

Measurements

Registration of age, ASA class, PS, comorbid conditions, computed tomography scans, primary tumor size, tumor growth rate, pathology parameters, observation time, survival time.

Results and limitations

Five-year overall survival (OS) and cancer-specific survival (CSS) rates were 42.8% and 93.3%, respectively. For tumors ≤4.0 cm in size, 5-yr CSS was 100%. Nine patients received delayed radical treatment, none of whom had later progression of the disease. In 18 patients histopathologic diagnosis of the renal masses were available, and in 15 patients (83%) renal cell carcinoma (RCC) was verified. The annual growth rate was <1 cm/yr in 85.4% of the cases. In tumors ≤4.0 cm, only 1 of 27 tumors (3.7%) grew faster than 1 cm/yr.

Conclusions

Management of renal masses by observation among older and comorbid patients seems to give acceptable results with regard to OS and CSS rates after 5 yr. The risk of disease progression is significantly higher in patients with larger sized renal masses (>4 cm). Thus, selection for observation in this group has to be stricter than in a group of patients with smaller sized renal masses (≤4.0 cm).     

Carbonic Anhydrase IX in Renal Cell Carcinoma: Implications for Prognosis,Diagnosis, and Therapy

Context

The clinical management of patients with renal cell carcinoma (RCC) remains difficult, and the development of new diagnostic, prognostic, and therapeutic tools is still required.

Objective

To review the current knowledge on the RCC-associated antigen carbonic anhydrase IX (CAIX) and provide evidence for how this antigen may aid in the clinical management of RCC.

Evidence acquisition

Clinical papers describing diagnostic, prognostic, and/or therapeutic applications of CAIX in RCC were selected from the Pubmed database. The search was manually augmented by reviewing the reference lists of articles.

Evidence synthesis

Expression of CAIX is regulated by the Von Hippel Lindau (VHL) protein (pVHL). Because of the invariable VHL mutational loss in clear-cell RCC (ccRCC) patients, CAIX expression is ubiquitous in ccRCC. Determination of CAIX expression in nephrectomy specimens of RCC patients improves prognostic accuracy; high CAIX expression appears to correlate with a favourable prognosis and a greater likelihood of response to systemic treatment for metastatic disease. Therefore, CAIX expression might be used to stratify metastatic ccRCC (mRCC) patients for systemic treatment. When incorporated into the RCC nomogram, CAIX expression seems to improve diagnostic accuracy for primary RCC as well as mRCC patients, but further evidence is required. Clinical studies with the CAIX-specific monoclonal antibody (mAb) cG250 have provided unequivocal evidence that ccRCC lesions can be imaged with radiolabeled cG250. Results are awaited of a large, randomised trial that aims to establish the value of cG250 imaging for primary RCC. The outcome of another large, placebo-controlled study is awaited to establish the usefulness of CAIX-targeted therapy in the adjuvant setting. Therapeutic trials with high-dose radiolabeled cG250 and CAIX-loaded dendritic cells in mRCC patients are still in phase 1 or 2.

Conclusions

CAIX improves diagnostic accuracy and is an attractive target for imaging of and therapy for ccRCC.     

A non-cancer-related survival benefit is associated with partial nephrectomy

Background

Partial nephrectomy (PN) may better protect against other-cause mortality (OCM) when compared with radical nephrectomy (RN) in patients with localized renal cell carcinoma (RCC).

Objective

Test the effect of treatment type on OCM.

Design, setting, and participants

Using the Surveillance Epidemiology and End Results–Medicare-linked database, 4956 RN patients (82%) and 1068 PN patients (18%) with T1a RCC were identified (1988–2005).

Measurements

To adjust for inherent differences between treatment types, we relied on propensity-matched analyses. One-to-one matching was performed according to age, sex, race, baseline Charlson comorbidity index (CCI), baseline diagnosis of hypercalcemia and hyperlipidemia, socioeconomic status (SES), population density, tumor size, and year of surgery. The 2- and 5-yr OCM rates were computed using cumulative incidence. Univariable and multivariable competing-risks regression analyses for prediction of OCM were performed according to treatment type. Adjustment was made for cancer-specific mortality (CSM), patient age, CCI, sex, race, SES, tumor grade, and year of surgery.

Results and limitations

Following propensity-based matching, 1068 RN patients were matched with 1068 PN patients. The 2- and 5-yr OCM rates after nephrectomy were 5.0% and 16.0% for PN versus 6.9% and 18.1% for RN, respectively. In the postpropensity multivariable analyses, patients who underwent PN were significantly less likely to die of OCM compared with their RN-treated counterparts (hazard ratio [HR]: 0.83; 95% confidence interval, 0.69–0.98; p = 0.04). Increasing age (HR: 1.08, p < 0.001), higher CCI (HR: 1.14, p < 0.001), female gender (HR: 0.79, p = 0.02), baseline hypercalcemia (HR: 2.05, p = 0.03), baseline hyperlipidemia (HR: 0.73, p = 0.003), and year of surgery (HR: 0.95, p = 0.003) were independent predictors of OCM.

Conclusions

Compared with PN-treated patients, RN-treated patients are more likely to die of OCM after surgery, even after adjusting for CSM, as well as baseline CCI. Consequently, PN should be offered whenever technically feasible.     

Laparoendoscopic single-site radical nephrectomy for renal cancer: technique and surgical outcomes

Background

Laparoendoscopic single-site (LESS) surgery has been developed in attempt to further reduce the morbidity and scarring associated with surgical intervention.

Objective

To describe the technique and report the surgical outcomes of LESS radical nephrectomy (RN) in the treatment of renal cell carcinoma.

Design, setting, and participants

LESS-RN was performed in 33 patients with renal tumours. The indications to perform a LESS-RN were represented by renal tumours not greater than T2 and without evidence of lymphadenopathy or renal vein involvement.

Surgical procedure

The Endocone (Karl Storz, Tuttlingen, Germany) was inserted through a transumbilical incision. A combination of standard laparoscopic instruments and bent grasper and scissors was used. The sequence of steps of LESS-RN was comparable to standard laparoscopic RN.

Measurements

Demographic data and perioperative and postoperative variables were recorded and analysed.

Results and limitations

The mean operative time was 143.7 ± 24.3 min, with a mean estimated blood loss of 122.3 ± 34.1 ml and a mean hospital stay of 3.8 ± 0.8 d. The mean length of skin incision was 4.1 ± 0.6 cm and all patients were discharged from hospital with minimal discomfort, as demonstrated by their pain assessment scores (visual analogue scale: 1.9 ± 0.8). The definitive pathologic results revealed a renal cell carcinoma in all cases and a stage distribution of four T1a, 27 T1b, and 2 T2 tumours. All patients were very satisfied with the appearance of the scars, and at a median follow-up period of 13.2 ± 3.9 mo, all patients were alive without evidence of tumour recurrence or port-site metastasis.

Conclusions

LESS is a safe and feasible surgical procedure for RN in the treatment of renal cell carcinoma and has excellent cosmetic results.     

Laparoscopic partial nephrectomy with segmental renal artery clamping: technique and clinical outcomes

Background

Warm ischemic injury is one of the most important factors affecting renal function in partial nephrectomy (PN). The technique of segmental renal artery clamping emerges as an alternative to conventional renal artery clamping for renal hilar control.

Objective

To evaluate the feasibility and efficiency of laparoscopic PN (LPN) with segmental renal artery clamping in comparison with the conventional technique.

Design, setting, and participants

A total of 75 patients underwent LPN from June 2007 to November 2009. All patients had T1a or T1b tumor in one kidney and a normal contralateral kidney. Thirty-seven patients underwent surgeries with main renal artery clamping, and 38 underwent surgeries with segmental artery clamping.

Intervention

All procedures were performed by the same laparoscopic surgeon.

Measurements

Blood loss, operation time, warm ischemia (WI) time, and complications affected renal function before and after operation were recorded.

Results and limitations

All LPNs were completed without conversion to open surgery or nephrectomy. The novel technique slightly increased WI time (p < 0.001) and intraoperative blood loss (p = 0.006), while it provided better postoperative affected renal function (p < 0.001) compared with the conventional technique. The total complication rate was 12%. Among the 38 cases where segmental renal artery clamping was performed, 7 had to convert to the conventional method. Tumor size and location influenced the number of clamped segmental arteries. Long-term postoperative renal function is still awaited.

Conclusions

LPN with segmental artery clamping is safe and feasible in clinical practice. It minimizes the intraoperative WI injury and improves early postoperative affected renal function compared with main renal artery clamping.     

Daily interruption of sedation in intensive care unit patients with renal impairment: remifentanil-midazolam compared to fentanyl-midazolam

Objective

We compared extubation time following daily interruption of sedation in intensive care unit patients with renal impairment with two sedation regimes remifentanil–midazolam and fentanyl–midazolam.

Study design

Prospective, randomized double-blind trial.

Patients and methods

Patients with renal impairment needing mechanical ventilation for more than 48 hours. Two groups: remifentanil (R) and fentanyl (F), Infusion rates were titrated to achieve the desired Ramsay score. The two groups received midazolam (2.5 mg then 0.1 mg/kg/h).

Results

Nineteen patients were included. Patient's characteristics, mean sedation time and sedation quality were comparable. Extubation time was significantly shorter in R group (1480 ± 980 versus 2880 ± 1280 min, P = 0.04). Weaning time was also shorter in R group (220 ± 164 versus 720 ± 480 min). Agitation on weaning was comparable in the two groups. Group R received significantly more morphine than group F after interruption of sedation.

Conclusion

Daily interruption of sedation with remifentanil is associated with shorter weaning and extubation time in patients with renal impairment. However further studies are necessary to determine if this issue is associated with lower rate of ventilation induced complications.     

Technique of Laparoscopic-Endoscopic Single-Site Surgery Radical Nephrectomy

Background

Laparoscopic-endoscopic single-site surgery (LESS) represents the closest surgical technique to scar-free surgery.

Objective

To assess the feasibility of LESS radical nephrectomy (LESS-RN).

Design, setting, and participants

Ten patients with body mass index (BMI) ≤30 underwent LESS-RN for renal tumour by two experienced laparoscopists.

Surgical procedure

TriPort (Olympus Winter &; Ibe, Hamburg, Germany) was inserted through a transumbilical incision. A combination of standard laparoscopic instruments and flexible grasper and scissors was used. A 5-mm 30° camera was also used. The standard laparoscopic transperitoneal nephrectomy technique was performed.

Measurements

Patient demographics, operative details, and final pathology were prospectively recorded. Postoperative evaluation of pain and use of analgesic medication were recorded.

Results and limitations

Ten cases were successfully accomplished (two right-sided tumours and eight left-sided tumours; tumour diameter ranges: 4–8 cm). The mean patient age was 63.5 yr (22–77 yr), and median BMI was 23.56 (18.2–26.6). The mean operative time was 146.4 min (120–180 min), and the mean blood loss was 202 ml (50–900 ml). Pathological examination observed organ-confined T1 renal cell carcinoma in nine cases and pT3b tumour in one case. One bleeding complication occurred. Limitations regarding the intraoperative instrument ergonomics and the requirement for ambidexterity of the surgeon were noted.

Conclusions

LESS-RN proved to be safe and feasible. Further clinical investigation in comparison to the established techniques should take place to evaluate the outcome of LESS-RN.     

Subclassification of pT3 urothelial carcinoma of the renal pelvicalyceal system is associated with recurrence-free and cancer-specific survival: proposal for a revision of the current TNM classification

Background

The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable.

Objectives

The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients.

Design, setting, and participants

From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

Intervention

RNU.

Measurements

Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses.

Results and limitations

Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p < 0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p = 0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p = 0.003) and cancer-specific mortality (HR: 1.7; p = 0.02). The major limitation is the retrospective character of the study.

Conclusions

Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer–International Union Against Cancer TNM classification system.     

Evaluation of NT-proBNP as an early biological marker of cardiac dysfunction in septic shock

Objective

To evaluate the NT-proBNP as a biological diagnosis marker of the myocardial dysfunction in septic shock.

Study design

Non-randomized prospective clinical study with written assent. The analysis of the data obtained was retrospective.

Patients and methods

All the patients with septic shock in the beginning of evolution (less than 24 h) were included. Patients with cardiac insufficiency, insufficient respiratory function and chronic renal insufficiency as well as cirrhotic patients were excluded. Among patients in shock, a NT-proBNP concentration measurement and a cardiac echography by transthoracic way were carried out at inclusion. The rates of NT-proBNP were compared with the data of the echography.

Results

Thirty-three patients in septic shock were included. On the whole of the collective, whether or not there is a cardiac dysfunction, the rates of NT-proBNP are not significantly different (11,306 ± 16,196 pg/ml versus 10,697 ± 12,346 pg/ml). By eliminating the patients with severe renal failure, we show that the NT-proBNP is non-significantly increased in the event of right and/or left ventricular failure (5751 ± 4180 pg/ml versus 1,256 ± 999 pg/ml).

Conclusion

The NT-proBNP can help to detect the cardiogenic share sometimes implied in the haemodynamic failure of the septic shock. However, because of the influence of the renal insufficiency and the respiratory, cardiologic and hepatic comorbidities on its secretion, its use cannot be recommended for patients in septic shock.     

Diagnostic and Prognostic Molecular Markers for Renal Cell Carcinoma: A Critical Appraisal of the Current State of Research and Clinical Applicability

Context

Earlier detection of renal cell carcinoma (RCC) and the recent expansion of treatment possibilities have positively influenced the outlook for patients with this disease. However, progression and treatment response are still not sufficiently predictable. Molecular markers could help to refine individual risk stratification and treatment planning, although they have not yet become clinically routine.

Objective

This review presents an overview of diagnostic and prognostic molecular markers for RCC and a subgrouping of these markers for different clinical issues.

Evidence acquisition

Literature and recent meeting abstracts were searched using these terms: renal (cell) carcinoma, molecular/tumor markers, biopsy, blood, urine, disease progression/prognosis, immunohistochemistry, risk factors, and survival.Due to the resulting large number of articles, studies were subjectively selected according to the importance of a study on the field, number of investigated patients, originality, multivariate analyses performed, contrast with previously published data, actuality, and assumed clinical applicability of the described results. More then 90% of the selected studies originated from the past 10 yr; >50% of the articles were written in 2006 or later.

Evidence synthesis

These data were predominantly obtained via nonrandomized, retrospective, but often controlled studies. Thereby, the resulting level of evidence is 2A/2B. The broad spectrum of described molecular markers (MMs) for RCC consists of markers already extensively studied in other malignancies (eg, p53), as well as MMs typically associated with specific RCC-altered gene functions and pathways (eg, von Hippel–Lindau [VHL]). The main goal of using MMs is to refine the prediction of clinical end points like tumor progression, treatment response, and cancer-specific and/or overall survival. Further, MMs might facilitate the clinical work-up of undefined renal masses and prove to be more convenient tools for screening and follow-up in blood and urine.

Conclusions

Presently, there are a number of promising MMs for diverse clinical questions, but the available data are not yet valid enough for routine, clinical application. We should comply with the demand for large multicenter prospective investigations, stratified for RCC type and treatment modalities, to lift the use of molecular markers in RCC to a practical level, thereby providing a better consultation for our patients regarding diagnosis, treatment, and follow-up.     

Adverse renal outcomes in subjects undergoing nephrectomy for renal tumors: a population-based analysis

Background

There has been increasing interest in determining renal outcomes after nephrectomy for renal tumors. Previous studies have not assessed all relevant risk factors, including proteinuria.

Objective

We sought to determine the risk and predictors for the development of adverse renal outcomes in a population-based cohort of subjects undergoing partial or complete nephrectomy.

Design, setting, and participants

A large population-based data set was used to identify all subjects undergoing nephrectomy in Alberta, Canada, from 2002 to 2007 using administrative codes. Comorbid conditions were determined using validated algorithms, and baseline estimated glomerular filtration rate (eGFR) and proteinuria status were determined.

Measurements

Postsurgical outcomes of end-stage renal disease, acute dialysis, chronic kidney disease (CKD) (eGFR <30 ml/min per 1.73 m²), and rapidly progressive CKD (eGFR <60 ml/min per 1.73 m² and eGFR loss ≥4 ml/min per 1.73 m² per year) were assessed. The risk and risk factors for developing the composite renal outcome were determined using a multivariable Cox proportional hazards model.

Results and limitations

Of 1151 subjects, 10.5% developed an adverse renal outcome over a mean of 32 mo. Complete (vs partial) nephrectomy was associated with a hazard ratio (HR) of 1.75 (95% confidence interval [CI], 1.02–2.99) for the primary outcome, as was lower baseline eGFR. Subjects with proteinuria were more likely to experience the primary outcome (42% vs 9%), conferring an adjusted HR of 2.40 (95% CI, 1.47–3.88).

Conclusions

Clinically important adverse renal outcomes are common in patients undergoing nephrectomy for renal tumors. In addition to baseline eGFR and the extent of the renal mass removed, proteinuria is a strong independent risk factor. Assessment of proteinuria, in addition to other risk factors, should be performed to inform prognosis and the optimal treatment strategy.