Riccardo Mastroianni

Editorial Comment to Robot‐assisted laparoscopic partial nephrectomy versus laparoscopic partial nephrectomy: A propensity score‐matched comparative analysis of surgical outcomes and preserved renal parenchymal volume

2016; 117: 126–30. 7 Wu Z, Li M, Song S et al. Propensity-score matched analysis comparing robot-assisted with laparoscopic partial nephrectomy. BJU Int. 2015; 115: 437–45. 8 Choi JE, You JH, Kim DK, Rha KH, Lee SH. Comparison of perioperative outcomes between robotic and laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur. Urol. 2015; 67: 891–901. 9 Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann. Surg. 2004; 240: 205–13. 10 Meeks JJ, Zhao LC, Navai N, Perry KT Jr, Nadler RB, Smith ND. Risk factors and management of urine leaks after partial nephrectomy. J. Urol. 2008; 180: 2375–8. 11 Matsuo S, Imai E, Horio M et al. Revised equations for estimated GFR from serum creatinine in Japan. Am. J. Kidney Dis. 2009; 53: 982–92. 12 Kondo T, Takagi T, Morita S et al. Early unclamping might reduce the risk of renal artery pseudoaneurysm after robot-assisted laparoscopic partial nephrectomy. Int. J. Urol. 2015; 22: 1096–102. 13 Gill IS, Desai MM, Kaouk JH et al. Laparoscopic partial nephrectomy for renal tumor: duplicating open surgical techniques. J. Urol. 2002; 167(2 Pt 1): 469–76. 14 Omae K, Kondo T, Takagi T et al. Renal sinus exposure as an independent factor predicting asymptomatic unruptured pseudoaneurysm formation detected in the early postoperative period after minimally invasive partial nephrectomy. Int. J. Urol. 2015; 22: 356–61. 15 Satkunasivam R, Tsai S, Syan S et al. Robotic unclamped “minimal-margin” partial nephrectomy: ongoing refinement of the anatomic zero-ischemia concept. Eur. Urol. 2015; 68: 705–12. 16 Shiroki R, Fukami N, Fukaya K et al. Robot-assisted partial nephrectomy: superiority over laparoscopic partial nephrectomy. Int. J. Urol. 2016; 23: 122–31. 17 Tanagho YS, Bhayani SB, Sandhu GS, Vaughn NP, Nepple KG, Figenshau RS. Renal functional and perioperative outcomes of off-clamp versus clamped robot-assisted partial nephrectomy: matched cohort study. Urology 2012; 80: 838–43. 18 Peyronnet B, Baumert H, Mathieu R et al. Early unclamping technique during robot-assisted laparoscopic partial nephrectomy can minimise warm ischaemia without increasing morbidity. BJU Int. 2014; 114: 741–7. 19 Zargar H, Akca O, Ramirez D et al. The impact of extended warm ischemia time on late renal function after robotic partial nephrectomy. J. Endourol. 2014; 29: 444–8. 20 Jang HJ, Song W, Suh YS et al. Comparison of perioperative outcomes of robotic versus laparoscopic partial nephrectomy for complex renal tumors (RENAL nephrometry score of 7 or higher). Korean J. Urol. 2014; 55: 808– 13. 21 Woldu SL, Thoreson GR, Okhunov Z et al. Comparison of renal parenchymal volume preservation between partial nephrectomy, cryoablation, and radiofrequency ablation. J. Endourol. 2015; 29: 948–55. 22 Zhang Z, Zhao J, Dong W et al. Acute kidney injury after partial nephrectomy: role of parenchymal mass reduction and ischemia and impact on subsequent functional recovery. Eur. Urol. 2016; 69: 745–52.

V8-12 COMBINING ANTEGRADE AND RETROGRADE DISSECTION DURING SALVAGE ROBOTIC RADICAL PROSTATECTOMY

INTRODUCTION AND OBJECTIVES: Despite primary treatment of prostate cancer with surgery or external radiation therapy, 2040% of patients relapse within 5 years and 25-35% progress to metastatic disease. Salvage lymph node dissection has been proposed in patients with biochemical recurrence from prostate cancer and nodal involvement only, although the optimal template remains a question of debate. Herein we describe the technique of robotic high-extended salvage retroperitoneal and pelvic lymphadenectomy (sRPLND+PLND) for “node-only” recurrent prostate cancer. METHODS: Twenty patients underwent robotic sRPLND+PLND for “node-only” recurrent prostate cancer after definitive primary treatment as identified by carbon-11 acetate PET/CT. Our anatomic template extends from bilateral renal artery and vein cranially up to Cloquets node caudally, completely excising lymphatic-fatty tissue from aorto-caval and iliac vascular trees. Meticulous node-mapping assessed nodes at 4 prospectively-assigned anatomic zones. RESULTS: Median age at salvage RPLND was 64 (45-76), median BMI was 26.4 kg/m2 (21.4 41.2), previous primary treatment was radical prostatectomy in 17 patients (85%) and external radiation therapy in 4 patients (15%), median time from primary treatment was 32 months (4-160) and median PSA at sRPLND+PLND was 2.1 ng/dl (0.28 38.17). Median operative time was 5 hours (3.5-5.8), blood loss was 100 ml (50-300), and hospital stay was 1 day (1-3). No patient had intra-operative complication, open conversion or blood transfusion. Four patients had Clavien II post-operative complications: flank/scrotal ecchymosis in 1 patient (5%), chylous ascites in 2 patients (10%) and neuropraxia/foot drop in 1 patient (5%). Final histology confirmed positive nodes in 16 patients (20%). Mean and median (range) number of nodes excised per patient was 89 and 80 (41-132) respectively. Mean and median (range) number of positive nodes was 21 and 6 (0-109) respectively. At 2 months post-operatively median (range) PSA was 0.76 ng/mL (<0.01-2 ng/mL). CONCLUSIONS: Herein we describe the detailed technique of robotic high-extended salvage RPLND+PLND for “node-only” recurrent prostate cancer and present the initial experience. Robotic sRPLND+PLND duplicates open surgery, with superior nodal counts and decreased morbidity compared to the published literature. Longer follow-up is necessary to assess oncologic outcomes.

PD61-11 THE NEW EPSTEIN GLEASON SCORE CLASSIFICATION SIGNIFICANTLY REDUCES UPGRADING IN PROSTATE CANCER PATIENTS

INTRODUCTION AND OBJECTIVES: Aim of our study was to evaluate differences between the old and the new classification systems in upgrading and downgrading rates in a cohort of patients undergoing radical prostatectomy (RP) for PCa. METHODS: Between 2012 and 2016, 636 patients with clinically localized PCa were treated with RP at two tertiary referral centers. Blood samples were collected and tested for total PSA. All the patients included in the study presented a biopsy performed in the same center where the RP was performed. Biopsy specimens as well as RP specimens were graded according to both 2005 Gleason and 2015 Epstein Gleason grading systems. Upgrading and downgrading rates on RP were recorded for both classifications and then compared. Clinically significant upgrading was defined as: Epstein score raising from 2 to 3 or from 3 to 5 and Gleason (2005) raising from 6 to 7 or from 7 to 9. As well clinically significant downgrading was defined as: Epstein score decreasing from 3 to 2 or from 5 to 3 and Gleason (2005) decreasing from 7 to 6 or from 9 to 7. The accuracy of the biopsy for each Gleason score classification was determined using the kappa coefficient of agreement: <0.4 poor agreement, 0.4-0.75 good agreement and > 0.75 excellent agreement. RESULTS: Median age and preoperative PSA levels were 66 years (IQR: 61-69) and 7.1 ng/ml (IQR: 5.2-10.0), respectively. Overall 247/636 (39 %) had advanced disease (pT 3a). Pathological grading of biopsies and RP specimens according to both classifications are described in table 1. The Epstein Gleason score presented a lower upgrading rate (93/636:15% vs 150/636:24%; p1⁄40.000) and a similar downgrading rate (36/636:6 % vs 28/636:4% p1⁄40.194) when compared to the 2005 one. The kappa-statistics measures of agreement between needle biopsy and RP specimens was better for the Epstein score when compared to the 2005 Gleason score (k1⁄4 0.569 0.034 vs k1⁄4 0.481 0.033). CONCLUSIONS: The new Epstein Gleason score classification significantly reduces upgrading events in patients with PCa treated with RP. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications particularly in PCa management. Further studies with a pathological review and reclassification of the specimens are needed to confirm our data.

PD29-06 ASSESSMENT OF LONG TERM FUNCTIONAL OUTCOMES IN MORE THAN 1000 PATIENTS TREATED WITH MINIMALLY ISCHEMIC PARTIAL NEPHRECTOMY

use nor type of HA was significantly associated with blood transfusion (p1⁄4.468 and p1⁄4.413, respectively), but they were associated with hemoglobin decline (p1⁄4.003 and p1⁄4.008, respectively). Other variables associated with hemoglobin decline were age, tumor size, RENAL score, estimated blood loss, and total intraoperative intravenous fluid volume. After adjusting for these factors, HA use was not significantly associated with postoperative hemoglobin decline (p1⁄4.942). Using multiple HA types was associated with a slightly increased hemoglobin decline (p1⁄4.035). Median cost of HA was

PD3-06 IMPACT OF PRIMARY HISTOLOGY ON DISEASE FREE SURVIVAL AFTER MINIMALLY INVASIVE ADRENALECTOMY FOR METASTATIC CANCER

234 per case (IQR

Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicentre prospective study

198-672). CONCLUSIONS: Hemostatic agents are costly and do not appear to be associated with improved outcomes, namely the need for transfusion or hemoglobin decline, following RPN. Prospective validation of these findings is warranted.

Papillary type 2 versus clear cell renal cell carcinoma: Survival outcomes

INTRODUCTION AND OBJECTIVES: Cushing’s syndrome is characterized by excess cortisol production from adrenocortical grand and presents various symptoms and signs. In corticotropin-independent Cushing’s syndrome, the excess cortisol production is attributed to an adrenocortical adenoma in the majority of cases, in which the underlying molecular pathogenesis has been poorly understood. METHODS: Somatic mutations in 8 adrenocortical tumors associated with corticotropin-independent Cushing’s syndrome was explored by whole exome sequencing, followed by target Sanger sequencing in an additional 57 cases. Functional impacts of detected mutations were also investigated by in vitro binding assays and assays for kinase activity. RESULTS: We identified novel hotspot mutation in PRKACA which encodes the catalytic subunit of cyclic AMP-dependent protein kinase (PKA). PRKACA mutations were found in 34 (52.3%) of 65 patients and invariably resulted in L206R variant protein. We also detected activating mutations of G-protein subunit as (GNAS) (R201C and R201H) in an additional 11 (16.9%) patients, which lead to constitutive accumulation of cAMP. Mutations in PRKACA and GNAS were completely mutually exclusive and accounted for 70% of samples had mutations in genes involved in the cAMP/PKA signaling pathway. The L206R PRKACA mutant abolished its binding to the regulatory subunit of PKA which inhibits catalytic activity of PKA and lead to constitutive, cAMP independent PKA activation. CONCLUSIONS: Corticotropin-independent Cushing’s syndrome is frequently associated with somatic mutations in PRKACA or GNAS. The current results highlight the major role of constitutive activation of the cAMP/PKA signaling pathway by somatic mutations in Corticotropin-independent Cushing’s syndrome and provide novel insight into the diagnosis and treatment of this unique syndrome.