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1 Financial and Other Disclosures Off-label use of drugs, devices, or other agents: None Data from IRB-approved human research is not presented I have the following financial interests or relationships to disclose: No financial relationships Disclosure code N Immatics BMY Aveo VVUS PTN Investor shareholder shareholder shareholder shareholder 1
2 RCC with level IV cava thrombus Markus Hohenfellner & Claudia Gasch Departement of Urology, University of Heidelberg Claudia Gasch
3 Events per 100,000 U.S. population RCC - SEER Datenbank 4 Incident cases Age related annual kidney cancer incidence stratified by tumor size Men 21 / 100,000 Women 10 / 100,000 Growing incidences of smaller tumors cm 2-4 cm 4-7 cm 7cm no "stage-shift" continous high incendence of large tumors Years Hollingsworth J M et al. JNCI J Natl Cancer Inst 2006;98:
4 Natural history of IVC tumor thrombus in RCC 5 RCC patients with tumor thrombus (4 clear cell / 1 papillary RCC) 59 years; 3 males, 2 females radical tumor surgery in Heidelberg tumor thrombus level: I=1, II=2, III=1, IV=1 Multiregion whole exome sequencing of primary tumor & tumor thrombus & normal tissue samples tumor thrombi contain viable & proliferating cells more proliferation of tumor thrombus cells than tumor cells unclear in which direction the tumor is growing limited mutational heterogeneity between tumor & thrombus signs for BRCAness with defects in other repair genes (AC3 signature) possible target for PARPis Genomic features of renal cell carcinoma with venous tumor thrombus. Warsow G,, Hohenfellner M, Duensing S. Sci Rep May 10;8(1):7477. doi: /s z
5 Tumor thrombus level vs. overall survival International Renal Cell Carcinoma Venous Thrombus Consortium 1122 patients, FU: 25 months median OS: 33.8 months median OS depends on thrombus level: RV: 45 months L1: 28 months L2: 21 months L3: 12 months Tumor thrombus level is an independent predictor of survival. L2 L3 L1 RV Martinez-Salamanca, Hohenfellner, Montorsi, Libertino et al., Eur Urol 59: 120 (2011)
6 Therapy conservative vs. surgery Longterm OS is only possible with surgery median OS: surgery 6.9 vs.19.8 months no surgery Haferkamp, Hohenfellner et al., J Urol 177: 1703 (2007)
7 Surgical complications Perioperative morbidity and mortality increases with IVC thrombus level IVC thrombus level Perioperative complications Total 12.5 % I 18 % II 20 % III 26 % IV 47% Karnes et al., Nat Clin Pract Urol 5:329 (2008); Lambert et al., Urology 69: 1054 (2007); Pouliot et al., J Urol 184:833 (2011); Cost et al., Eur Urol 59: 912 (2011)
8 Preoperative planning & arrangements High quality cross-sectional imaging - MRI superior to CT (CAVE: filling artefacts) Cardiologic (+TEE) & anaesthesiologic assessment of the patient Interdisciplinary planning & preparation of the procedure (Urology, Cardiothoracic Surgery, Anaesthesiology, Radiology, General Surgery) Preoperative embolization Transoesophageal echocardiography (TEE) during surgery Heart-lung machine, Cardio technician & Cardiothoracic surgeon in stand by Hofer L, Gasch C, Hohenfellner M.et al, Level-IV-Cavathrombus, Urologe A. (2017)
9 Preoperative renal artery embolization (PRAE) Evidence: No randomized data available Retrospective studies regarding PRAE supporting different extremes Heidelberg experience: PRAE immediately preoperative Rationale: allows direct management of tumor thrombus without necessity to physically manipulate the kidney first Lardas M, Stewart F, et al; Eur Urol Aug Prospective Heidelberg Tumor Data Bank
10 Intraoperative transesophageal ultrasound Exact definition of IVC thrombus level during surgery Real-time control of the tumor thrombus Change of surgical strategy, if needed
11 IVC tumor thrombus level IV: personalized surgical technique Heidelberg Heart-lung machine in stand-by Transesophageal ultrasound Incision: Chevron ± sternotomy Accurate dissection of the IVC Mobilizing the liver to the left, presentation of retrohepatic IVC Main principles: Mobilizing the thrombus to an infradiaphragmatic position Tourniquet placement below hepatic veins
12 Heidelberg data RCC patients with IVC thrombus level IV & surgery between at the University Hospital of Heidelberg (n = 41) Surgery n = 28 CPB n = 10 (36%) no CPB n = 18 (64 %) Infradiaphragmatic clamping Digital reposition (via atriotomy) Fogarty-Catheter Manual reposition (via atrial compression)
13 Individual approach 1. Infradiaphragmatic clamping Manual mobilisation infradiaphragmatically Blood ± incision loss L (median) of diaphragma 4,8 ± mobilisation pericardium Thrombus fixation with tourniquet Thrombectomy via cavotomy (± IVC resection or patch) n = 8 Surgery time in min (median) 284 Blood transfusions (median) 8,5 Length of stay postop in d (median) 14,5 Survival in Mo (median) 22,1 30-day mortality 1 (12,5%) Cianco et al, Ann Thorac Surg 89:505 11; (2010)
14 Digital reposition of thrombus Sternotomy n = 5 Surgery time in min (median) 362 Purse-string suture of right atrium Blood loss in L (median) 8 Atriotomy + insertion of index finger Blood transfusions (median) 18 Length of stay postop in d (median) 16 Palpation + repositioning of thrombus Thrombus fixation with tourniquet Survival in mo (median) 16,1 30-day Thrombectomy mortality via abdominal approach 0 Schneider, Hohenfellner et al, Urology 2013
15 Fogarty catheter Insertion of Fogarty-Catheter in Surgery IVC via time confluence in min (median) of gonadal vein 283 Mobilising the thrombus infradiaphragmatically while using Blood transfusions (median) 10 TEE Thrombus fixation with tourniquet Thrombectomy via cavotomy n = 4 Blood loss in L (median) 3,8 Length of stay in d (median) 23,5 Survival in Mo (median) n/a 30-day mortality 0 12 F - Reliant Stent Graft Ballon Catheter; Medtronic Vascular
16 Case report 02/2013 Fogarty catheter approach 70 year-old female, RCC left kidney & IVC tumor thrombus (Level IV) Nephrectomy & thrombectomy using Fogarty catheter approach on Feb. 26th d1 postop: back from ICU to urology ward Drain removal on d3 & d7 postop Discharge on day 9 after surgery LoS: Feb. 24th March 7th, 2013 (11 d)
17 Individual approach 4. Manual reposition (via atrial compression) Sternotomy n = 1 Surgery time in min (median) 255 Dissection of intrapericardial IVC Blood loss in L (median) 5,0 Palpation + repositioning of thrombus Blood transfusions (median) 10 in the atrium without atriotomy Length of stay in d (median) 17 Thrombus fixation with tourniquet Survival in Mo (median) n/a Thrombectomy via abdominal approach 30-day mortality 0
18 Individual approach Cardiopulmonary Bypass CPB mandatory, if: Thrombus of the pulmonary artery Infiltration of the atrium Residual thrombi
19 Individual approach Cardiopulmonary Bypass CPB mandatory, if: Thrombus of the pulmonary artery Infiltration of the atrium Residual thrombi
20 Cardiopulmonary Bypass Heidelberg data n = 10 Surgery time in min (median) 270 Blood loss in L (median) 6,0 Blood transfusions (median) 16,5 Length of stay in d (median) 18 Survival in Mo (median) 23,9 30-day mortality 0
21 Laparoscopy in level IV tumor thrombus? Laparoscopic & robotic tumor thrombectomies (Level I-III) are increasingly performed over the last years (Gill IS et al, 2015 & 2016) Less experience with laparoscopy in level IV tumor thrombi 1 study from Nanjing (n=5) with right RCC Laparoscopic & thoracoscop.-assist. open atriotomy for thrombectomy CPB & hypothermia (33-35 C) Clamping of infrarenal IVC, left renal vein & hepatoduodenal ligament and SVC Can be safely perfomered, but technical limitations, if e.g. left kidney tumor (patient repositioning!) or caval wall invasion of tumor Shao P et al. Eur Urol Jul;68(1):
22 How about Robotics? No studies have been published to level IV IVC thrombus so far but there are case reports in the news of Keck Medicine of USC (Gill I & Cunningham M, April 2017)
23 Take home messages RCC patients with vast IVC invasion profit of surgical treatment. No general surgical strategy - several preoperative benchmarks define the individual approach. Individual techniques without CPB can be safely performed and should be preferred. Interdisciplinary planning & performance Intraoperative versatility
24
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