A. Mari

The Role of M1 and M2 Macrophages in Prostate Cancer in relation to Extracapsular Tumor Extension and Biochemical Recurrence after Radical Prostatectomy

Introduction. The aim of our work was to investigate the causal connection between M1 and M2 macrophage phenotypes occurrence and prostate cancer, their correlation with tumor extension (ECE), and biochemical recurrence (BR). Patient and Methods. Clinical and pathological data were prospectively gathered from 93 patients treated with radical prostatectomy. Correlations of commonly used variables were evaluated with uni- and multivariate analysis. The relationship between M1 and M2 occurrence and BR was also assessed with Kaplan-Meier survival analysis. Results. Above all in 63.4% there was a M2 prevalence. M1 occurred more frequently in OC disease, while M2 was more represented in ECE. At univariate analysis biopsy and pathologic GS and M2 were statistically correlated with ECE. Only pathologic GS and M2 confirmed to be correlated with ECE. According to macrophage density BCR free survival curves presented a statistically significant difference. When we stratified our population for M1 and M2,we did not find any statistical difference among curves. At univariate analysis GS, pTNM, and positive margins resulted to be significant predictors of BCR, while M1 and M2 did not achieve the statistical significance. At multivariate analysis, only GS and pathologic stage were independent predictors of BR. Conclusion. In our study patients with higher density of M count were associated with poor prognosis; M2 phenotype was significantly associated with ECE.

Simple enucleation versus standard partial nephrectomy for clinical T1 renal masses: Perioperative outcomes based on a matched-pair comparison of 396 patients (RECORd project)

OBJECTIVES To compare simple enucleation (SE) and standard partial nephrectomy (SPN) in terms of surgical results in a multicenter dataset (RECORd Project). MATERIALS AND METHODS patients treated with nephron sparing surgery (NSS) for clinical T1 renal tumors between January 2009 and January 2011 were evaluated. Overall, 198 patients who underwent SE were retrospectively matched to 198 patients who underwent SPN. The SPN and SE groups were compared regarding intraoperative, early post-operative and pathologic outcome variables. Multivariable analysis was applied to analyze predictors of positive surgical margin (PSM) status. RESULTS SE was associated with similar WIT (18 vs 17.8 min), lower intraoperative blood loss (177 vs 221 cc, p = 0.02) and shorter operative time (121 vs 147 min; p < 0.0001). Surgical approach (laparoscopic vs. open), tumor size and type of indication (elective/relative vs absolute) were associated with WIT >20 min. The incidence of PSM was significantly lower in patients treated with SE (1.4% vs 6.9%; p = 0.02). At multivariable analysis, PSM was related to the surgical technique, with a 4.7-fold increased risk of PSM for SPN compared to SE. The incidence of overall, medical and surgical complications was similar between SE and SPN. CONCLUSIONS Type of NSS technique (SE vs SPN) adopted has a negligible impact on WIT and postoperative morbidity but SE seems protective against PSM occurrence.

Simple enucleation for the treatment of highly complex renal tumors: Perioperative, functional and oncological results.

AIM To assess the role of simple enucleation (SE) for the treatment of highly complex renal tumors. METHODS Overall, 96 Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification score 10 to 13 renal tumors were treated with SE at our institution. All conventional perioperative variables, surgical, functional and oncological results were gathered in a prospectively maintained database. Survival curves were generated using a Kaplan-Meier method. Univariate analysis assessed the outcome differences. RESULTS Mean (± 1s.d.) clinical tumor diameter was 4.8 (± 1.6 cm). 70.8% of patients had ≥ cT1b stage. The PADUA score was recorded as 10, 11, 12 and 13 in 57.3%, 29.2%, 11.5%, and 2.1% of tumors respectively. Overall, 76 patients were treated with an open approach and 20 robotically. Mean warm ischemia time (WIT) was 19.2 min, and WIT greater than 25 min occurred in 14.6% of cases. Positive surgical margin (PSM) rate was 3.6% and trifecta was achieved in 64.3% of patients. Postoperative surgical complications occurred in 24% of patients, with 14.6% Clavien-Dindo grade 1-2, 8.3% grade 3, and 1% grade 4. Five-year cancer specific survival (CSS), recurrent free survival (RFS), and overall survival (OS) rates resulted 96.1%, 90.8% and 88.0%, respectively. Overall, 4.2% of patients experienced progressive disease. At follow-up, the mean decrease of eGFR from preoperative value was 13.9 ml/min. This was not significantly correlated with PADUA score (p = 0.69). The surgical approach was neither a predictor of Trifecta outcome, nor of postoperative complications, WIT > 25 min or PSM rate. CONCLUSIONS SE is an effective treatment for highly-complex renal tumors, with a potential key role to widen the NSS (nephron sparing surgery) indications according to guidelines.

Partial Nephrectomy in Clinical T1b Renal Tumors: Multicenter Comparative Study of Open, Laparoscopic and Robot-assisted Approach (the RECORd Project).

OBJECTIVE To evaluate perioperative results of open (OPN), laparoscopic (LPN), and robot-assisted partial nephrectomies (RAPN) and to identify predictive factors of Trifecta achievement for clinical T1b renal tumors in a multicenter prospective dataset. METHODS Data of 285 patients who had OPN (133), LPN (57), or RAPN (95) for cT1b renal tumors were extracted from the RECORd Project. High-volume centers were defined as ≥50 overall cases of partial nephrectomy per year. Trifecta was defined as simultaneous absence of perioperative complications, negative surgical margins, and ischemia time <25 minutes. RESULTS The 3 groups had comparable body mass index, preoperative hemoglobin, creatinine and estimated glomerular filtration rate, tumor clinical diameter, and growth pattern. LPN and RAPN were more frequently exclusive of high-volume centers. RAPN showed significantly lower median estimated blood loss compared with OPN and LPN. Trifecta was achieved in 62.4%, 63.2%, and 69.5% of OPN, LPN, and RAPN (P = NS) cases. Median warm ischemia time (WIT) was significantly shorter during OPN than during LPN and RAPN. RAPN had significantly shorter WIT compared with LPN. RAPN was significantly less morbid than OPN regarding intraoperative and postoperative complications. LPN (1.9%) and RAPN (2.5%) showed a lower rate of positive margins compared with OPN (6.8%) (P = NS). At multivariable analysis, exophytic tumor growth pattern, estimated blood loss, and high-volume centers were significant predictive factors for Trifecta achievement. CONCLUSION Clinically, T1b renal tumors suitable for NSS can be safely treated by LPN or RAPN in high-volume centers. RAPN allows for significantly lower WIT and estimated blood loss with higher rate of Trifecta achievement compared with LPN.

TriMatch comparison of the efficacy of FloSeal versus TachoSil versus no hemostatic agents for partial nephrectomy: Results from a large multicenter dataset

To evaluate the efficacy of hemostatic agents, TachoSil and FloSeal, during partial nephrectomy using a large multicenter dataset.

A snapshot of nephron-sparing surgery in Italy: A prospective, multicenter report on clinical and perioperative outcomes (the RECORd 1 project)

INTRODUCTION Nephron-sparing surgery (NSS) has become the standard of care for the surgical management of small and clinically localized renal cell carcinoma (RCC). The conservative management of those RCCs is increasing over time. Aim of this study was to report a snapshot of the clinical, perioperative and oncological results after NSS for RCC in Italy. MATERIAL AND METHODS We evaluated all patients who underwent conservative surgical treatment for renal tumours between January 2009 and December 2012 at 19 urological Italian Centers (RECORd project). Perioperative, radiological and histopathological data were recorded. Surgical eras (2009 vs 2012 and year periods 2009-2010 vs 2011-2012) were compared. RESULTS Globally, 983 patients were evaluated. More recently, patients undergoing NSS were found to be significantly younger (p = 0.05) than those surgically treated in the first study period, with a significantly higher rate of NSS with relative and imperative indication (p < 0.001). More recently, a higher percentage of procedures for cT1b or cT2 renal tumours was observed (p = 0.02). Utilization rate of open partial nephrectomy (OPN) constantly decreased during years, laparoscopic partial nephrectomy (LPN) remained almost constant while robot-assisted partial nephrectomy (RAPN) increased. The rate of clampless NSS constantly increased over time. The use of at least one haemostatic agent has been significantly more adopted in the most recent surgical era (p < 0.001). CONCLUSIONS The utilization rate of NSS in Italy is increasing, even in elective and more complex cases. RAPN has been progressively adopted, as well as the intraoperative utilization of haemostatic agents and the rate of clampless procedures.

Robotic vs open simple enucleation for the treatment of T1a-T1b renal cell carcinoma: a single center matched-pair comparison.

OBJECTIVE To compare surgical, pathological, short-term functional data, and complications of endoscopic robotic-assisted simple enucleation (ERASE) and open simple enucleation (OSE). METHODS We undertook matched-pair analysis (age, tumor size, and preoperative aspects and dimensions used for an anatomical [PADUA] score) of 392 patients treated with simple enucleation (SE) for T1a-T1b renal tumors in our department, including 160 patients in the OSE group and 80 in the ERASE group. Perioperative outcomes were compared with univariate analysis. Variables associated with warm ischemia time (WIT) >25 minutes, complications, and postoperative acute kidney dysfunction (AKD) were assessed with multivariate analysis. RESULTS The groups were comparable in body mass index (BMI), comorbidity, and preoperative renal function. In the ERASE vs the OSE group, no significant differences resulted regarding WIT (18.5 vs 16.4 minutes, P = .5), complications, transfusion rate, reoperation rate for Clavien grade ≥ 3 complications, and positive surgical margin rate (2.9% vs 2.1%, P = .63). In elective patients, no significant difference resulted in variation of estimated glomerular filtration rate from baseline (8.5 vs 13.9 mL/min, P = .17) and AKD. In the ERASE group, the clamping of renal pedicle was used with a lower frequency (P <.0001), with lower estimated blood loss (EBL), longer operative time, and a 1-day shorter hospitalization (P = .001). On the multivariate analysis, the surgical approach was not independently associated with WIT >25 minutes, postoperative complications, and AKD. CONCLUSION The ERASE is a feasible technique with a positive surgical margin rate comparable to OSE; it showed WIT and complication rates similar to the open approach, along with the advantages of mini-invasivity.

A Prospective, Multicenter Evaluation of Predictive Factors for Positive Surgical Margins After Nephron-Sparing Surgery for Renal Cell Carcinoma: The RECORd1 Italian Project

BACKGROUND The purpose of this study was to evaluate the predictors of positive margins in one of the largest available prospective multi-institutional studies. PATIENTS AND METHODS We evaluated all patients who underwent NSS for radiologically diagnosed kidney tumors between January 2009 and December 2012 at 19 urological Italian centers (Registry of Conservative Renal Surgery [RECORd] project). Preoperative and anthropometric data, comorbidities, intraoperative and postoperative outcomes, and histological findings were analyzed. The negative and PSMs were compared according to the clinical and surgical variables. Multivariable logistic regression models were applied to analyze predictors of PSMs. RESULTS Eight hundred consecutive patients were evaluated. Seven hundred sixty-one (95.1%) and 39 patients (4.9%) achieved negative and PSMs, respectively. Patients with PSMs were significantly older compared with those with negative margins (median age: 66.6 vs. 61.8 years, respectively; P = .001). A higher incidence of PSMs was observed when NSS was performed for renal masses located in the upper pole (P = .001). A lower rate of PSMs was found in patients treated with simple enucleation rather than standard PN (1.6% vs. 7.4%, respectively; P < .0001). A greater incidence of PSMs was found in Fuhrman 3/4 tumors (11.3%; P < .0001). At multivariable analysis, age (odds ratio [OR], 1.04; P = .01), upper pole tumor location (OR, 2.85; P = .005), standard PN (OR, 3.45; P = .004), and Fuhrman 3-4 nuclear grade (OR, 4.81; P = .001) were found to be independent predictors of PSMs. CONCLUSION In our multi-institutional report, young age, simple enucleation, middle or lower tumor location, and low-grade tumor were demonstrated to be independent predictors of negative SMs.

Positive surgical margins and local recurrence after simple enucleation and standard partial nephrectomy for malignant renal tumors: Systematic review of the literature and meta-analysis of prevalence

INTRODUCTION The definition of the safest width of healthy renal margin to achieve oncological efficacy and therefore of the safest resection technique (RT) during partial nephrectomy (PN) continues to be widely debated. The aim of this study is to evaluate the prevalence of positive surgical margins (PSM), loco-regional recurrence (LRR) and renal recurrence (RER) rates after simple enucleation (SE) and standard partial nephrectomy (SPN) for malignant renal tumors. EVIDENCE ACQUISITION A systematic review of the English-language literature was performed through August 2016 using the Medline, Web of Science and Embase databases according to the PRISMA criteria. A systematic review and meta-analysis was performed in those studies that defined the exact anatomical location of recurrence after PN. EVIDENCE SYNTHESIS Overall, 33 studies involving 11,282 patients were selected for quantitative analysis. At a median follow-up of 43 (SE) and 52 (SPN) months, the pooled estimates of the prevalence of PSMs, LRR and RER were 2.7% (95% CI: 1.5-4.6%, P<0.001) and 0.4% (95% CI: 0.1-2.2%, P=0.018), 2.0% (95% CI: 1.4-2.8%, P<0.001) and 0.9% (95% CI: 0.5-1,7%, P=0.04), 1.5% (95% CI: 0.9-2.3%, P=0.001) and 0.9% (95% CI: 0.5-1,7%, P=0.40) in patients undergoing SPN and SE, respectively. CONCLUSIONS Our systematic analysis and meta-analysis demonstrates that SE is noninferior to SPN regarding PSM, LRR and RER rates in patients undergoing PN for malignant renal tumors. Further studies using standardized reporting tools are needed to evaluate the role of resection techniques for oncologic outcomes after PN.

Role of Clinical and Surgical Factors for the Prediction of Immediate, Early and Late Functional Results, and its Relationship with Cardiovascular Outcome after Partial Nephrectomy: Results from the Prospective Multicenter RECORd 1 Project

Purpose: We sought to determine the predictors of short‐term and long‐term renal function impairment after partial nephrectomy. Materials and Methods: Clinical data on 769 consecutive patients who underwent partial nephrectomy were prospectively recorded at a total of 19 urological Italian centers from 2009 to 2012 in the RECORd 1 (Italian Registry of Conservative Renal Surgery) Project. We extracted clinical data on 708 of these patients who were alive, free of recurrent disease and with a minimum 2‐year functional followup. Results: Of the patients 47.3% underwent open, 36.6% underwent laparoscopic and 16.1% underwent robot‐assisted partial nephrectomy. The median baseline estimated glomerular filtration rate was 84.5 ml/minute/1.73 m2 (IQR 69.9–99.1). Immediate (day 3 postoperatively), early (month 1) and late (month 24) renal function impairment greater than 25% from baseline was identified in 25.3%, 21.6% and 14.8% of cases, respectively. Female gender and the baseline estimated glomerular filtration rate were independent predictors of immediate, early and late renal function impairment. Age at diagnosis was an independent predictor of immediate and late impairment. Uncontrolled diabetes was an independent predictor of late impairment only. Open and laparoscopic approaches, and pedicle clamping were independent predictors of immediate and early renal function impairment. Overall 58 of 529 patients (11%) experienced postoperative cardiovascular events. Body mass index and late renal function impairment were independent predictors of those events. Conclusions: Surgically modifiable factors were significantly associated with worse immediate and early functional outcomes after partial nephrectomy while clinically unmodifiable factors affected renal function during the entire followup. Late renal function impairment is an independent predictor of postoperative cardiovascular events.