Are warm ischemia and ischemia time still predictive factors of poor renal function after partial nephrectomy in the setting of elective indication?

PURPOSE: To evaluate renal function and to identify factors associated with renal dysfunction in the elective indications setting of nephron-sparing surgery (NSS). METHODS: We retrospectively reviewed operative data and glomerular filtration rate (GFR) of 519 patients treated by NSS in an elective indications setting between 1984 and 2006 in eight academic institutions. A GFR decrease under the thresholds of 60 or 45 ml/min at last follow-up was considered a significant renal dysfunction. Univariate and multivariate regression models were used to assess multiple factors of renal function. RESULTS: Median age, tumor size, preoperative, and final GFR were 59.5 years (27-84), 2.7 cm (0.9-11), 79 (45-137), and 69 ml/min (p < 0.0001), respectively, with a median follow-up of 23 months (1-416). Hilar clamping was performed in 375 procedures (72.3 %). Significant GFR decrease was observed in 89 patients (17.1 %). Median operating time, hilar clamping duration, and blood loss were 137 min (55-350), 22 min (0-90), and 150 ml (0-4150), respectively. At univariate analysis, age (p = 0.002), preoperative GFR (p = 0.001), pedicular clamping (p = 0.01), and ischemia time (p = 0.0001) were associated with renal dysfunction. Age (p = 0.004; HR 1.2), pedicular clamping (p = 0.04; HR 1.3), and ischemia time (p = 0.0001; HR 1.8) remained independent risk factors for renal function deterioration in multivariate analysis. CONCLUSION: Non- or time-limited clamping techniques are associated with preservation of renal function in the elective indications setting of NSS.

The use of partial nephrectomy: results from a contemporary national prospective multicenter study.

PURPOSE: Despite benefits in functional renal outcome and favorable oncological efficacy, previous studies show marked underuse of partial nephrectomy (PN). We investigated national utilization of partial and radical nephrectomy (RN) using a contemporary, prospective population-based cohort. METHODS: Between June and December 2010, 1,237 patients were treated by PN or RN for renal cell carcinoma in 56 French centers. Data were prospectively collected, and statistical analyses were performed. RESULTS: Overall, 667 (53.9 %) and 570 patients (46.1 %) underwent RN and PN, respectively. In case of PN, surgical approach was an open PN in 63.3 % of cases, a laparoscopic PN in 21.0 % of cases and a robot-assisted PN in 15.7 % of cases. PN was used in T1a, T1b, T2 and T3 tumors in 395 (76.7 %), 131 (38.2 %), 29 (14.7 %) and 7 (4.6 %), respectively. Median ischemia time was 16 min [0-60], and mean blood loss was 280.4 ml (±339.9). Tumor characteristics and operative features were significantly different according to the surgical approach. Warm ischemia time was significantly higher in case of laparoscopic or robot-assisted procedure (p < 0.001). There was no statistical significant difference in blood loss and transfusion rate according to surgical approach. Postoperative medical and surgical complications occurred in 8.2 and 10.0 % of PN, respectively, with no significant difference according to surgical approach. CONCLUSIONS: Partial nephrectomy for renal cell carcinoma is commonly used in this French centers sample. Mini-invasive approaches represent also a significant part of all partial nephrectomies with no difference in terms of complication rates.

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.

[Partial nephrectomy by selective renal parenchymal clamping using a new clamp]. / Néphrectomie partielle par clampage parenchymateux sélectif utilisant un nouveau clamp.

OBJECTIVE: To study the results of open partial nephrectomy by selective renal parenchymal clamping using a new renal parenchyma clamp, the Réniclamp. MATERIAL AND METHODS: Partial nephrectomy was performed in 37 patients using the Réniclamp for an imperative indication in 7 patients (solitary kidneys) and an elective indication in 30 patients. The tumour was situated in a pole in 22 cases and on the lateral border of the kidney in 15 cases. The mean tumour diameter was 29 mm (range: 10 - 60 mm). RESULTS: The mean operating time was 147 minutes and the mean clamping time was 25 minutes. Mean blood loss was 191 cc (range : 50-450 cc) and no patient required blood transfusion. No cases of slipping of the clamp or renal parenchymal lesion due to the clamp were observed. COMPLICATIONS: A urinary fistula treated by endoscopy and obstructive clot of the upper urinary tract, which required endoscopic treatment and selective embolisation. The surgical margins were negative in every case. CONCLUSION: Partial nephrectomy by selective renal parenchymal clamping is an alternative to the pedicle clamping technique in almost every case of renal tumour except for central renal lesions. Réniclamp distributes the pressure homogeneously, avoiding damage to the parenchyma due to excess pressure on the proximal part of the clamp and bleeding due to insufficient pressure on the distal part of the clamp.

[Comparison of open and laparoscopic partial nephrectomy: a French multicentre experience]. / Comparaison de la néphrectomie partielle par voie laparoscopique et par voie ouverte: une expérience multicentrique française.

OBJECTIVES: To compare open (OPN) and laparoscopic (LPN) partial nephrectomy (PN) techniques in the light of a French multicentre series. MATERIAL AND METHODS: Data corresponding to 741 PN (91 laparoscopic and 650 open procedures) were compared in terms of the indications, tumour diameter, operative data, complication rates and length of hospital stay. RESULTS: Tumours were smaller in the LPN group (2.7 vs 3.4 cm, p = 0.001). There were fewer malignant tumours (71.1% vs 80% p = 0.05) and fewer NP by necessity (20.9% vs 31.4%. p = 0.04) in the LPN group than in the OPN group. There were fewer hilar tumours in the LPN group than in the OPN group (LPN: 4% vs OPN: 14.8%, p = 0.03). Pedicle clamping was performed less frequently in the LPN group (33% vs 50.2%, p = 0.002) but for a significantly longer mean duration (35 minutes vs 19 minutes, p = 0.0001). The mean operating time was longer in the LPN group (163 vs 150 minutes, p = 0.02). The surgical complication rate (17.6% vs 14.3%), transfusion rate (6.6% vs 10.5%) and mean blood loss (363 vs 434 ml) were not significantly different between the 2 groups. There were significantly more urinary fistulas (12.1% vs 2.5%, p < 0.001) and medical complications (24.2% vs 14%, p = 0.01) in the laparoscopy group, but, in the longer-term, urinarvfistula rates were comparable in the 2 groups. The length of hospital stay was shorter for LPN (9.1 vs 11.2 days, p = 0.009). CONCLUSION: This comparative series, reflecting initial experience, shows that laparoscopic partial nephrectomy achieves similar operative and perioperative results to those of open partial nephrectomy. However, the indications for laparoscopic partial nephrectomy remain selective, as the pedicle clamping time and medical complication rates are higher with laparoscopic surgery. Experience and technical progress in laparoscopic partial nephrectomy should make the operative technique comparable to that of open surgery.

The effect of gender and age on kidney cancer survival: younger age is an independent prognostic factor in women with renal cell carcinoma.

OBJECTIVE: Gender-specific differences in incidence of renal cell carcinoma (RCC) and its outcome have previously been reported. We used age as a surrogate to test whether this might be hormone-related in a large international RCC cohort. METHODS AND MATERIALS: This study included patients treated by nephrectomy at 10 international academic centers. Clinicopathologic features were assessed using chi-square and the Student t-tests. Kaplan-Meier survival estimates and Cox proportional hazards models addressed the effect of gender and age on disease-specific survival. RESULTS: Of the 5,654 patients, 3,777 (67%) were men and 1,877 (33%) were women. Generally, women presented at lower T stages (P<0.001), had fewer metastases (P<0.001), and had lower-grade tumors (P<0.001). Women more frequently had clear-cell (87% vs. 82%) and less frequently had papillary RCC (7% vs. 12%) than men (P<0.001). Women had a 19% reduced risk of death from RCC than men (hazard ratio 0.81, 95% confidence interval 0.73-0.90, P<0.001). The survival advantage for women was present to the greatest degree in the age group<42 years (P = 0.0136) and in women aged 42 to 58 years (P<0.001), but was not apparent in patients aged 59 years and older (P = 0.248). Age was an independent predictor of disease-specific survival in women (hazard ratio 1.011, 95% confidence interval 1.004-1.019, P = 0.004), but not in men. CONCLUSIONS: As a group, women present with less advanced tumors, leading to a 19% reduced risk of RCC-specific death compared with men. This survival difference is present only in patients aged<59 years. Because this gender-based survival difference is not related to pathologic features, the role of hormonal effects on the development and progression of RCC needs to be investigated.

Nephron-sparing surgery is superior to radical nephrectomy in preserving renal function benefit even when expanding indications beyond the traditional 4-cm cutoff.

OBJECTIVES: To analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in preserving renal function outcome in relation to tumor size indication. METHODS AND MATERIALS: Clinical data from 973 patients operated at 9 academic institutions were retrospectively analyzed. Glomerular filtration rate (GFR) before and after surgery was calculated with the abbreviated Modification of the Diet in Renal Disease equation. For a fair comparison between the 2 techniques, all imperative indications for PN were excluded. A shift to a less favorable GFR group following surgery was considered clinically significant. RESULTS: Median age at diagnosis was 60 years (19-91). Tumor size was smaller than 4 cm in 665 (68.3%) cases and larger than 4 cm in 308 (31.7%) cases. PN and RN were performed in 663 (68.1%) and 310 (31.9%) patients, respectively. In univariate analysis, patients undergoing PN had a smaller risk for developing significant GFR change following surgery than those undergoing RN did. This was true for tumors≤4 cm (P = 0.0001) and for tumors>4 cm (P = 0.0001). In multivariate analysis, the following criteria were independent predictive factors for developing significant postoperative GFR loss: the use of RN (P = 0.0001), preoperative GFR<60 ml/min (P = 0.0001), tumor size≥4 cm (P = 0.0001), and older age at diagnosis (P = 0.0001). CONCLUSIONS: The renal function benefit carried out by elective PN over RN persists even when expanding nephron-sparing surgery indications beyond the traditional 4-cm cutoff.

Nephron-sparing surgery for renal tumors measuring more than 7 cm: morbidity, and functional and oncological outcomes.

BACKGROUND: The purpose of this study was to evaluate morbidity, functional, and oncological outcomes after NSS in renal tumors > 7 cm. MATERIALS AND METHODS: We retrospectively analyzed data from 168 patients with tumors > 7 cm who were treated using NSS between 1998 and 2012. RESULTS: Imperative and elective indications accounted for 76 (45.2%) and 92 (54.8%) patients, respectively. Major perioperative complications and renal function deterioration occurred in 33 (19.6%) and 51 patients (30.4%), respectively. In multivariate analysis, age older than 60 years (P = .001; hazard ratio [HR], 5) and tumor malignancy (P = .014; HR, 6.7) were prognostic factors for renal function deterioration whereas imperative indication was a risk factor for major postoperative complications (P = .0019; HR, 2.7). In 126 (75%) patients with malignant tumors, after a median follow-up of 30 months (range, 1-254 months), 25 patients (20.2%) died. In multivariate analysis, imperative indication (P = .023; HR, 4.2), positive surgical margin (P = .021; HR, 3.3), and Fuhrman grade > II (P = .013; HR, 3.7) were prognostic indicators for cancer-free survival (CFS). Imperative indication (P = .04; HR, 8.5) and Fuhrman grade > II (P = .04; HR, 3.9) were predictive factors of cancer-specific survival (CSS). In case of elective indication, positive surgical margin, local recurrence, and cancer-related death occurred in 4 (7.6%), 1 (1.1%), and 1 (1.1%) cases, respectively. For elective indication, 5-year estimates of CFS, CSS, and overall survival rates were: 85.7%, 98%, and 93.9%, respectively. CONCLUSION: In this selected population, imperative vs. elective indication status seems to play a critical role in oncologic outcomes. Oncologic results for elective indications are close to those reported with radical nephrectomy.

Predictive factors for ipsilateral recurrence after nephron-sparing surgery in renal cell carcinoma.

BACKGROUND: Ipsilateral recurrence after nephron-sparing surgery (NSS) is rare, and little is known about its specific determinants. OBJECTIVE: To determine clinical or pathologic features associated with ipsilateral recurrence after NSS performed for renal cell carcinoma (RCC). DESIGN, SETTING, AND PARTICIPANTS: We analysed 809 NSS procedures performed at eight academic institutions for sporadic RCCs retrospectively. MEASUREMENTS: Age, gender, indication, tumour bilaterality, tumour size, tumour location, TNM stage, Fuhrman grade, histologic subtype, and presence of positive surgical margins (PSMs) were assessed as predictors for recurrence in univariate and multivariate analysis by using a Cox proportional hazards regression model. RESULTS AND LIMITATIONS: Among 809 NSS procedures with a median follow-up of 27 (1-252) mo, 26 ipsilateral recurrences (3.2%) occurred at a median time of 27 (14.5-38.2) mo. In univariate analysis, the following variables were significantly associated with recurrence: pT3a stage (p=0.0489), imperative indication (p<0.01), tumour bilaterality (p<0.01), tumour size >4cm (p<0.01), Fuhrman grade III or IV (p=0.0185), and PSM (p<0.01). In multivariate analysis, tumour bilaterality, tumour size >4cm, and presence of PSM remained independent predictive factors for RCC ipsilateral recurrence. Hazard ratios (HR) were 6.31, 4.57, and 11.5 for tumour bilaterality, tumour size >4cm, and PSM status, respectively. The main limitations of this study included its retrospective nature and a short follow-up. CONCLUSIONS: RCC ipsilateral recurrence risk after NSS is significantly associated with tumour size >4cm, tumour bilaterality (synchronous or asynchronous), and PSM. Careful follow-up should be advised in patients presenting with such characteristics.

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.

Metachronous bilateral renal cell carcinoma: risk assessment, prognosis and relevance of the primary-free interval.

PURPOSE: We evaluated the prognosis, risk factors and relevance of the primary-free interval in a large cohort with metachronous bilateral renal cell carcinoma. MATERIALS AND METHODS: We studied 120 patients with metachronous, bilateral renal cell carcinoma who were treated at 12 international academic centers. Logistic regression was performed to evaluate risk factors for contralateral metachronous renal cell carcinoma during followup. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median age at diagnosis of the first and second renal cell carcinomas was 54 and 62 years, respectively. The most common histological subtype was bilateral clear cell renal cell carcinoma (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was found in 81%. The 15-year disease specific survival rates for the first and second renal cell carcinomas were 66% and 44%, respectively. Logistic regression revealed von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age as independent risk factors for contralateral renal cell carcinoma after surgery for unilateral renal cell carcinoma. A longer primary-free interval was associated with a better prognosis. When calculating disease specific survival from the diagnosis of the first renal cell carcinoma, the primary-free interval was an independent prognostic factor. CONCLUSIONS: Long-term survival rates of metachronous, bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age are independent risk factors for contralateral renal cell carcinoma. These risk factors support close and extended abdominal surveillance following nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary-free interval have a more favorable prognosis.

Morbidity and clinical outcome of nephron-sparing surgery in relation to tumour size and indication.

OBJECTIVE: To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication. METHODS: The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancer-specific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using chi(2) (Fischer exact test) and Student t tests, respectively. RESULTS: A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4+/-2.1cm. In 730 elective procedures mean operative time (p=0.002), mean blood loss (p=0.01), the need for blood transfusion (p=0.001), and urinary fistula rate (p=0.01) were significantly increased for tumours >4 cm. However, these differences did not result in significantly increased medical (p=0.4), surgical complication rates (p=0.6), or length of hospital stay (p=0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumours < or =4 cm and >4 cm. CONCLUSION: Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours >4 cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity.

Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an international multicentre experience.

OBJECTIVE: To present a multicentre experience and the largest cohort to date of nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because it is rare the single-institutional experience is limited. PATIENTS AND METHODS: We retrospectively studied 10 337 patients from 12 urological centres to identify patients with N0M0 synchronous bilateral RCC; the clinicopathological features and cancer-specific survival were compared to a cohort treated for N0M0 unilateral RCC. RESULTS: In all, 153 patients had synchronous bilateral solid renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell RCC was the major histological subtype (76%), and papillary RCC was the next most frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group performance status (ECOG PS) and T classification, but bilateral RCCs were more frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19% vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC had a similar prognosis (P = 0.63); multifocality did not affect survival (P = 0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman grade, but not laterality, as independent prognostic factors for cancer-specific survival. CONCLUSIONS: Patients with N0M0 synchronous bilateral RCC and N0M0 unilateral RCC have a similar prognosis. The frequency of a familial history for RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in bilateral synchronous than in unilateral RCC. The significant pathological findings in synchronous bilateral RCC are papillary subtype and multifocality.