Thierry Dujardin

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.

The Impact of Solitary and Multiple Positive Surgical Margins on Hard Clinical End Points in 1712 Adjuvant Treatment–Naive pT2–4 N0 Radical Prostatectomy Patients

BACKGROUND Positive surgical margins (PSMs) increase the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), but their impact on hard clinical end points is a topic of ongoing discussion. OBJECTIVE To evaluate the influence of solitary PSMs (sPSMs) and multiple PSMs (mPSMs) on important clinical end points. DESIGN, SETTING, AND PARTICIPANTS Data from 1712 patients from the Centre Hospitalier Universitaire de Québec with pT2-4 N0 prostate cancer (PCa) and undetectable prostate-specific antigen after RP were analyzed. INTERVENTION RP without neoadjuvant or adjuvant treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Kaplan-Meier analysis estimated survival functions, and Cox proportional hazards models addressed predictors of clinical end points. RESULTS AND LIMITATIONS Median follow-up was 74.9 mo. A total of 1121 patients (65.5%) were margin-negative, 281 patients (16.4%) had sPSMs, and 310 patients (18.1%) had mPSMs. A total of 280 patients (16.4%) experienced BCR, and 197 patients (11.5%) were treated with salvage radiotherapy (SRT). Sixty-eight patients (4.0%) received definitive androgen deprivation therapy, 19 patients (1.1%) developed metastatic disease, and 15 patients (0.9%) had castration-resistant PCa (CRPC). Thirteen patients (0.8%) died from PCa, and 194 patients (11.3%) died from other causes. Ten-year Kaplan-Meier estimates for BCR-free survival were 82% for margin-negative patients, 72% for patients with sPSMs, and 59% for patients with mPSMs (p<0.0001). Time to metastatic disease, CRPC, PCa-specific mortality (PCSM), or all-cause mortality did not differ significantly among the three groups (p=0.991, p=0.988, p=0.889, and p=0.218, respectively). On multivariable analysis, sPSMs and mPSMs were associated with BCR (hazard ratio [HR]: 1.711; p=0.001 and HR: 2.075; p<0.0001), but sPSMs and mPSMs could not predict metastatic disease (p=0.705 and p=0.242), CRPC (p=0.705 and p=0.224), PCSM (p=0.972 and p=0.260), or all-cause death (p=0.102 and p=0.067). The major limitation was the retrospective design. CONCLUSIONS In a cohort of patients who received early SRT in 70% of cases upon BCR, sPSMs and mPSMs predicted BCR but not long-term clinical end points. Adjuvant radiotherapy for margin-positive patients might not be justified, as only a minority of patients progressed to end points other than BCR. PCSM was exceeded 15-fold by competing risk mortality.

Multivariate analysis of the factors involved in loss of renal differential function after laparoscopic partial nephrectomy: a role for warm ischemia time

BACKGROUND Partial nephrectomy (PN) is now the gold standard for the surgical treatment of small renal masses. We evaluated the effect of WIT and other factors on RDF assessed by preoperative and postoperative renal scintigraphy. METHODS Between 2003 and 2008, 182 consecutive laparoscopic PN (LPN) were performed in an academic centre. Among those, 56 had mercaptoacetyl triglycine (MAG3) lasix renal scintigraphy preoperatively and postoperatively. RESULTS Medians for age, preoperative estimated glomerular filtration rate and computed tomography scan tumour size were 62 years, 82 mL/min/1.73m(2) and 26 mm, respectively. Median WIT and preoperative RDF were 30 minutes and 50%, respectively. Median loss of RDF after surgery was 14%. Linear regression curves showed that loss in RDF rate was 0.2% per minute when WIT was <30 minutes and 0.7% per minute when WIT was ≥30 minutes. In multivariate analysis, length of WIT and endophytic tumour location were associated with a statistically significant loss of RDF (p < 0.05), but only in the group who experienced >30 minutes of WIT. INTERPRETATION Our results suggest that the factors associated with loss of RDF are not the same before and after 30 minutes of WIT and that the rate of loss in RDF increases after 30 minutes. Since, the effect of WIT is small up to 30 minutes, we believe that surgery should focus on limiting the resection of normal parenchyma and to ensure negative margins and hemostasis, rather than on premature unclamping.

Determination of Success by Objective Scintigraphic Criteria After Laparoscopic Pyeloplasty

BACKGROUND AND PURPOSE Laparoscopic pyeloplasty (LP) is a minimally invasive technique with high success rates that match open procedures. There are a variety of success definitions. We have defined and reported our success rate by objective renal scintigraphic criteria. We also compare our scintigraphic success with clinical success defined by absence of pain. PATIENTS AND METHODS We reviewed retrospectively 111 adult cases of laparoscopic pyeloplasties. The Anderson-Hynes technique was used in 98% of cases. nonprimary pyeloplasties represented 12 cases of our series. Renal scintigraphic success rates were defined as: strict (T(1/2) <10 min), nonobstructive (T(1/2) <20 min), and technical success (improved T(1/2)). Of our patients, 83% had renal scintigraphy before and after surgery. RESULTS Average operative time was 128 +/- 45 minutes, blood loss was 52 +/- 168 mL, and median postoperative hospital stay was 3 days. After surgery, T(1/2) was decreased by 26 minutes for a median time of 13 minutes. Strict success was achieved in 61% of cases, while nonobstructive success and technical success were achieved in 86% and 93%, respectively. No difference in success was observed between primary and nonprimary cases. Clinical success (absence of symptoms) was achieved in 95% of LPs. We also show that 75% of patients who had obstruction after LP based on scintigraphic criteria were asymptomatic, showing a poor correlation between symptoms and obstruction. CONCLUSIONS By defining success with renal scintigraphic criteria, we still obtain a high success rate. When using strict criteria, however, the success decreases and might identify patients at risk of late recurrence.

Chylous ascites as a complication of laparoscopic donor nephrectomy.

Laparoscopic living donor nephrectomy (LLDN) is a minimally invasive technique for kidney procurement and was developed with the hope of reducing the disincentives associated with live renal donation. Compared with open donor nephrectomy (ODN), this alternative has many advantages including less postoperative pain and earlier return to work. Unfortunately, these benefits are sometimes negated by postoperative complications. Among these, chylous ascites (CA) is a rare but serious problem that is usually managed conservatively. We report the case of a living donor who developed CA refractory to initial conservative management and surgical treatment. We also discuss the role of surgery in the treatment of CA following LLDN.

FDG-PET/CT for pre-operative staging and prognostic stratification of patients with high-grade prostate cancer at biopsy

BackgroundThe role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in prostate cancer (PCa) has not been well defined yet. Because high-grade PCa tends to exhibit increased glycolytic rate, FDG-PET/CT could be useful in this setting. The aim of this study was to assess the value of FDG-PET/CT for pre-operative staging and prognostic stratification of patients with high-grade PCa at biopsy.MethodsFifty-four patients with a Gleason sum ≥8 PCa at biopsy underwent FDG-PET/CT as part of the staging workup. Thirty-nine patients underwent radical prostatectomy (RP) and pelvic lymph node (LN) dissection, 2 underwent LN dissection only, and 13 underwent non-surgical treatments. FDG-PET/CT findings from clinical reports, blinded reading and quantitative analysis were correlated with clinico-pathological characteristics at RP.ResultsSuspicious foci of increased FDG uptake were found in the prostate, LNs and bones in 44, 13 and 6% of patients, respectively. Higher clinical stage, post-RP Gleason sum and pattern, and percentage of cancer involvement within the prostate were significantly associated with the presence of intraprostatic FDG uptake (IPFU) (P < 0.05 in all cases). Patients without IPFU who underwent RP were downgraded to Gleason ≤7 in 84.6% of cases, as compared to 30.8% when IPFU was reported (P = 0.003). Qualitative and quantitative IPFU were significantly positively correlated with post-RP Gleason pattern and sum, and pathological T stage. Absence and presence of IPFU were associated with a median 5-year cancer-free survival probability of 70.2 and 26.9% (P = 0.0097), respectively, using the CAPRA-S prognostic tool.ConclusionThese results suggest that, among patients with a high-grade PCa at biopsy, FDG-PET/CT could improve pre-treatment prognostic stratification by predicting primary PCa pathological grade and survival probability following RP.

Prospective study comparing two techniques of renal clamping in laparoscopic partial nephrectomy: impact on perioperative parameters.

PURPOSE To compare en bloc and artery-only clamping techniques on renal function and perioperative outcomes after laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS From March 2003 to December 2008, 205 patients underwent LPN by one surgeon in a single institution. The first 103 LPNs were achieved with artery-only clamping (AO), and the last 102 LPNs were realized under control of the renal hilum (artery and vein [AV] clamping). Renal function was evaluated by creatinine changes, estimation of the glomerular filtration rate (eGFR), and assessment of split renal function using renal mercaptoacetyl triglycine-Lasix scintigraphy. Sixty-two of 205 patients had renal scintigraphy before and after surgery. RESULTS There was no significant difference between the two groups regarding demographic data and renal mass characteristics. Warm ischemia time (WIT) was higher in the AO group: 30.4 ± 8.2 vs 23.3 minutes ± 10.0 (P<0.0001). The eGFR change was significantly lower in the AV group during the postoperative period: 10.2 mL/min vs 13.7 mL/min (P=0.0472). Operative blood loss, operative time, and complication rate were not statistically different between groups. Average loss of differential function of the operated kidney was 13.6 ± 9.2% for the AO group and 14.3 ± 12.3% for the AV group (P=0.8016). On multivariate analysis, clamping technique was not a predictive factor of renal function reduction. CONCLUSION AV and AO techniques are associated with similar renal function outcomes in patients who were undergoing LPN. In our series, the AV technique was associated with a lower WIT, an important predictor of decrease in renal function.

Prognostic value of urinary prostate cancer antigen 3 (PCA3) during active surveillance of patients with low-risk prostate cancer receiving 5α-reductase inhibitors

To determine the clinical performance of the urinary prostate cancer antigen 3 (PCA3) test to predict the risk of Gleason grade re‐classification amongst men receiving a 5α‐reductase inhibitor (5ARI) during active surveillance (AS) for prostate cancer.

Cystatin C for early detection of acute kidney injury after laparoscopic partial nephrectomy

Introduction and Objectives: Mortality due to AKI has not changed significantly over the past 50 years. This is due in part to failure to detect early AKI and to initiate appropriate therapeutic measures. There is therefore a need to identify biomarkers that would improve the early detection of AKI. The objective of this study was to assess whether cystatin C levels obtained at specific timepoints during laparoscopic partial nephrectomy (PN) could be early predictors of AKI. Materials and Methods: Twenty-five patients underwent laparoscopic PN for organ-confined tumors. All procedures were performed by two surgeons in a single institution. Plasma samples were collected preoperatively, and post-unclamping at 5, 20, 120 min and on the day following surgery. Plasma cystatin C was measured by enzyme-linked immunosorbent assay. Correlation between levels of cystatin C and other parameters of interest were assessed in order to define cystatin C ability to predict AKI and loss of renal function following laparoscopic PN. Results: The mean baseline eGFR was 93 ml/min/1.73 m2. Warm ischemia time varied between 16 and 44 min. Post-operative day 1 (POD1) cystatin C levels compared to baseline were increased in 13 (52%) of the patients. There was a high correlation between the difference of POD 1 and baseline value, and eGFR in the immediate postoperative period (r = −0.681; P = 0.0002) and at 12-month follow-up (r = −0.460, P = 0.048). However, the variation in cystatin C levels at earlier timepoints were not associated to AKI nor renal function. Conclusions: High increase in POD 1 cystatin C levels from baseline may help identify patients with AKI and those at higher risk of chronic kidney disease, following laparoscopic PN.

EVALUATION OF FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY ASSOCIATED WITH COMPUTED TOMOGRAPHY (18F-FDG-PET/CT)IMAGING FOR STAGING OF BLADDER TRANSITIONAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: PET with 18F-FDG has been considered of limited value because of the urinary excretion of the tracer. The purpose of this study was to investigate the role of PET associated with Computed Tomography (CT) in the staging of new diagnosed bladder cancer (BC) or in restaging of BC during follow-up after cystectomy or chemotherapy using furosemide and oral hydration to remove the excreted 18-F-FDG from the bladder. METHODS: Thirty two patients (23 male, 9 female), with histologically proven muscle invasive BC by transurethral resection of the bladder (TUR/B), were included in this prospective study. Mean age was 69 years and mean follow up was of 4,7 months (0,3-10,3). All underwent a 18F-FDG from head to the upper thighs with additional pelvic images after 1 h I.V. furosemide and oral hydration at least 3 months after TUR/B. In 25 cases a CT of thorax and abdomen with contrast medium had also been preformed within the 2 weeks prior to PET/CT. For CT scan, nodes greater than 1 cm or defined as suspicious by the radiologist were considered positive. The 18F-FDG-PET/CT lesions with metabolic activity greater than 2.5 SUV on a confirmed anatomical structure were considered positive. Imaging findings were confirmed by histology or if not possible, by imaging follow-up. RESULTS: Of the 32 patients, 26 patients were studied with 18F-FDG-PET/CT before radical cystectomy or in 2 cases only pelvic lymphadenectomy. In the same group, 19 CT were also performed. 18F-FDG-PET/CT detected 21 of the 23 bladder lesions (91,3%) and 8/15 (53,3%) pelvic node metastasis, mostly N2. False negative were a pTis and a pT4. CT detected 12 of 17 bladder lesion (70.6%) and 4 out of 9 positive nodes (44.4%). 18F-FDG-PET/CT showed prostate metabolic activity in 4 cases. In 2 cases BC invasion was histologically proven. Metabolic activity was seen in 2 para-aortic lymph-nodes (LN), 3 mediastinal LN, 2 cervical LN and 4 pulmonary nodules. All these lesions showed progression on imaging follow up. CT was negative in all prostate lesions, 1 para-aortic LN and 2 pulmonary nodules. CONCLUSIONS: This prospective series shows that 18F-FDGPET/CT with furosemide wash out of the bladder was better than conventional CT for the detection of residual tumor in the bladder, pelvic LN metastasis and prostate infiltration. Moreover PET/CT detected earlier than conventional CT distant metastasis to retroperitoneal and cervical LN and pulmonary metastasis.