Pilot study comparing the two hemostatic agents in patients undergoing partial nephrectomy

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1 Palacios et al. BMC Research Notes 2013, 6:399 RESEARCH ARTICLE Oen Access Pilot study comaring the two hemostatic agents in atients undergoing artial nehrectomy Diego Aguilar Palacios 1, Michael McDonald 2, Makito Miyake 1 and Charles J Rosser 1,3* Abstract Background: Recently studies have demonstrated imroved outcomes in atients undergoing nehron-saring surgery (NSS) for low stage renal tumors, thus NSS is widely acceted as the treatment otion for these atients. With NSS, there is a risk of renal hemorrhage and thus haemostatic agents may be routinely alied to the cut surface of the kidney. Herein we comare two commercially available haemostatic agents alied intra-oeratively to the cut surface of the kidney. Post-oerative outcomes (oncologic and non-oncologic) are reorted. Methods: The medical records of 23 atients with susicious renal mass documented on axial imaging and who underwent oen NSS via a mini-subcostal incision were extensively reviewed. One of two haemostatic agents (, n = 11; Arista W, n = 12) was intra-oeratively alied to the cut surface of the kidney. Chi-square and T- student test was used to comare outcomes between the of 11 atients who had and the 12 atients who had Arista W. Results: Median re-oerative size of renal mass was 4.3 cm (range cm). Final athology revealed 3 oncocytomas and 20 renal cell carcinoma (17 clear cell, 1 chromohobe and 2 aillary), T1a = 14 and T1b = 6. Mean intra-oerative blood loss and hosital stay between the vs. Arista W s did not significantly differ (227 ml vs. 250 ml, = 0.68 and 4.4 days vs. 4.5 days, = 0.76, resectively). Intra-oerative and ost-oerative comlications were not different between the two s. No recurrences have been documented with a mean follow-u of 18 months. Conclusion: Along with meticulous surgical technique, the use of either haemostatic agent ( or Arista W )was not associated with high rate of intra-oerative or ost-oerative haemorrhage. Thus either haemostatic agent may be successfully used during NSS. Keywords: Haemostatic agent, Nehrectomy, Nehron-saring, Partial, Renal mass Background In 2012, it is estimated that 64,770 Americans will be diagnosed with cancer of the kidney resulting in aroximately 13,570 deaths [1]. Interestingly, kidney cancer is one of only a few cancers with an increasing incidence over the ast two decades [2]. Renal cell carcinoma (RCC) accounts for over 85% of all kidney tumors, which makes u 2-3% of all adult malignancies [3]. Aroximately, 70% of RCCs are incidentally discovered on axial imaging of the abdomen with >50% of RCCs being * Corresondence: deacdoc@aol.com 1 Section of Urologic Oncology, MD Anderson Cancer Center Orlando, Orlando, FL 32806, USA 3 Cancer Research Institute, Orlando Health, 6900 Lake Nona Blvd, Orlando, FL 32527, USA Full list of author information is available at the end of the article low-stage (T1-T2 N0M0) [4,5]. Desite advancements in drug discovery for advanced RCC, mortality rates have not changed over the ast two decades [6], however for atients with low-stage disease, surgical extiration offers excellent 5-year survival rates of 95% [5]. Traditionally, surgical exiration of these low-stage tumors was in the form of radical nehrectomy (i.e., removal of kidney, Gerota s fascia and isilateral adrenal gland) [7]. Then contemorary studies demonstrate that in select tumors, adrenal saring surgery [8] and nehron saring surgery (NSS) [9] could be effectively erformed without comromising oncologic outcomes. Recently studies have demonstrated imroved non-oncological outcomes in atients undergoing NSS for low-stage tumors [10]. Thus, we currently find ourselves in the midst of a new era in 2013 Palacios et al.; licensee BioMed Central Ltd. This is an Oen Access article distributed under the terms of the Creative Commons Attribution License (htt://creativecommons.org/licenses/by/2.0), which ermits unrestricted use, distribution, and reroduction in any medium, rovided the original work is roerly cited.

2 Palacios et al. BMC Research Notes 2013, 6:399 Page 2 of 5 the management of low-stage kidney cancer, where NSS is center stage and widely acceted as the treatment otion for these atients. It is not unusual to use haemostatic agents during rocedures with a roensity for bleeding. NSS is one of these rocedures. Numerous haemostatic agents are available for use. One such agent that has been widely used over the ast decade is. consists of atented bovine-derived gelatin granules coated in human-derived thrombin that work in combination to form a stable clot at the bleeding site [11]., FDA aroved in 1999, exands aroximately 20% within about 10 minutes, giving redictable control during and after surgery [12]. Another haemostatic agent, Arista W, is a synthetic haemostatic comound that includes an absorbable haemostatic owder consisting of Microorous Polysaccharide Hemosheres (MPH W ). Arista works through accelerating the intrinsic clotting cascade by extracting fluid from blood, concentrating serum roteins and latelets, which is the scaffolding for the formation of a fibrin clot [13]. Earlier studies reorted relatively high comlication rates associated with NSS [14], which have greatly reduced over the ast decade due to surgical refinement [15,16]. One such comlication was haemorrhage related to the surgery (intrao-erative or ost-oerative). Thus the successful incororation of a haemostatic agent, which may be routinely alied to the cut surface of the kidney, may rove to be advantageous. Herein we comare two commercially available haemostatic agents alied intraoeratively. Intra-oerative and ost-oerative outcomes (oncologic and non-oncologic) are reorted. Method After MD Anderson Cancer Center Orlando institutional review board aroval with consent waiver, medical records of atients who had undergone NSS for a susicious renal mass from December 2009 to Setember 2012 were extensively reviewed. Preferentially, nonhilar, renal lesions < 7 cm were considered for NSS. Using these selection criteria, our study was comrised of 23 atients who underwent NSS. Clinical and hosital records were reviewed for demograhics, smoking history, body mass index (BMI), comorbidities, reoerative and ost-oerative glomerular filtration rate (GFR), intra-oerative features, disease characteristics and outcomes (oncologic and non-oncologic). All atients had renal masses visualized and characterized by axial imaging (CT scan = 20, MRI scan = 2 and CT scan/mri scan = 1). Of the 23 atients with renal masses, 3 renal masses were noted to be cystic masses (Bosniak III = 2, size 3 cm and 5 cm and Bosniak IV = 1, mean size 5.5 cm), while the remainder was solid. Aroximately four weeks rior to NSS, atient had serum creatinine drawn and GFR was calculated. In three of the 23 atients, a ercutaneous core biosy of the renal mass was erformed demonstrating RCC (Clear cell carcinoma = 2 and aillary carcinoma = 1). All atients underwent oen mini-incision NSS. Oen NSS was erformed as reviously described [17] with modification by one surgeon (CJR). Briefly, the renal artery was clamed and renal arenchyma was transected and the tumor excised with grossly negative surgical margins. The surgical secimen was roerly orientated and sent immediately to athology for frozen section analysis, confirming negative surgical margins of at least 1 mm. Next the argon beam laser was used to extensively coagulate the cut surface of the renal cortex. The incision of the kidney (cortex and medullae) was then comletely covered by either 5 ml of in 11 atients which was the agent of choice from December 2009 to February 2011 or 3 grams of Arista W in 12 atients which was the agent of choice from March 2011 to the resent. Into the renal defect, a large ledget of Surgicel W was laced. Vertical mattress sutures, incororating the Surgicel W ledget, was laced to close the renal defect. Comlications were graded with Clavien-Dindo Classification and were noted to be either intra-oerative or ost-oerative. Post-oerative comlications were classified as urological and nonurological (e.g., cardiac, gastrointestinal ulmonary, thromboembolic, incisional or other). Urological comlication was defined as significant hemorrhage > 500 ml necessitating intervention or transfusion, urine leakage (drainage of greater than 50 ml daily for more than one week with fluid biochemistry comatible with urine) and acute renal failure (resulting in any dialysis, ureteral obstruction or kidney loss) [10]. In addition, serum creatinine levels were assessed four week after surgery and ost-oerative GFR was calculated. Chi-square and T- student test was used to comare outcomes between the of 11 atients who had and the 12 atients who had Arista W. P s less than 0.05 were considered to be statistically significant. All data were analyzed using SPSS software version 22. Results Demograhics, laboratory s and disease characteristics of the entire are summarized in Table 1. The mean age of the entire was 57.9 ± 10.4 years. The majority of atients were male (57%), Caucasian (52%) with left-sided lesions (78%). Median re-oerative size of renal mass measured on axial imaging was 4.3 cm (range cm). Mean BMI was 30.2 ± 4.5 kg/m 2 and mean re-oerative GFR was 82.0 ± 19.2 ml/min/1.73 m 2.Regarding these demograhics, laboratory s and disease

3 Palacios et al. BMC Research Notes 2013, 6:399 Page 3 of 5 Table 1 Demograhics and reoerative data Variable Mean age (±SD, years) 57.9 ± ± 9.6 Arista W 60.5 ± Male:female 13:10 7:4 6:6.51 Race 0.40 Caucasian 12 (52%) 5 (46%) 7 (58%) African American 3 (13%) 1 (8%) 2 (17%) Latinos 7 (31%) 5 (46%) 2 (17%) Others 1 (4%) 0 (0%) 1 (8%) Tobacco history 12 (52%) 6 (55%) 6 (50%) 0.82 Mean BMI (± SD, kg/m 2 ) 30.2 ± ± 2.8 Mean Preoerative GFR (±SD, ml/min/1.73 m 2 ) 82.0 ± ± ± ± Side of renal mass (R/L) 5/18 1/10 4/ Median size of renal mass (cm) 4.3 (range, ) Table 2 Oncologic and functional outcomes Variable 4.4 ± ± Arista W Histology 0.34 Clear cell 17 9 (82%) 8 (66%) (74%) Paillary 2 (9%) 0 (%) 2 (17%) Chromohone 1 (4%) 1 (9%) 0 (0%) Oncocytoma 3 (13%) 1 (9%) 2 (17%) Pathologic stage 0.86 T1a 14 7 (70%) 7 (70%) (70%) T1b 6 (30%) 3 (30%) 3 (30%) Furhman grade (40%) 6 (60%) 2 (20%) (40%) 7 (70%) (55%) 3 1 (5%) 0 (0%) 1 (10%) 4 0 (0%) 0 (0%) 0 (0%) Pos. surgical margin N.A. 0 (0%) 0 (0%) 0 (0%) Mean ost-oerative GFR (ml/ min/1.73 m 2 ) 70.9 ± ± ± Hosital stay/days 4.5 ± ± ± characteristics, the vs. Arista W grous did not differ significantly. The median cool ischemia time was 30.8 minutes in the grou comared to 35.4 minutes in the Arista W grou ( = 0.075). Mean intra-oerative blood loss was 227 ml in the grou comared to 250 ml in the Arista W grou ( = 0.68). Post-oerative disease characteristics and laboratory s of the entire are summarized in Table 2. The majority of atients had clear cell variant of RCC (74%), athologic stage T1a (70%) and Fuhrman grade 2 (55%). The reviously described Bosniak cysts were found to be clear cell RCC. Disease characteristics were similar between the two grous. Mean ost-oerative GFR was 66.9 ± 21.8 ml/min/1.73 m 2 in the Floseal and 74.5 ± 15.4 ml/min/1.73 m 2 in the Arista grou, = 0.34). Mean hosital stay between the vs. Arista W s did not significantly differ (4.4 days vs. 4.5 days, = 0.76, resectively). Seven comlications (two intra-oerative and five ostoerative) were noted in 6 (26%) of the atients. The two intra-oerative comlications included transfusion for 500 ml blood loss (Clavien II) and small isilateral neumothorax (Clavien I). The nuemothorax was managed conservatively with comlete resolution noted over two weeks. The five ost-oerative comlications included rolonged urinary leak of 10 days (Clavien I) and readmission with 30 days for chest ain (Clavien I) (both in one atient), ileus = 1 (Clavien II), and >25% reduction in GFR-2 = 2 (Clavien I) (Table 3). No difference was noted in ost-oerative comlications in atients in the grou comared to the Arista W grou. No ost-oerative mortalities were noted. No recurrences have been documented with a mean follow-u of 18 months. Discussion Nehron-saring surgery was initially used to treat atients with anatomically or functionally solitary kidney, bilateral renal masses or hereditary renal cell carcinoma or atients affected by comorbidities that might imair renal function, such as diabetes, hyertension, atherosclerosis, calculous renal disease, chronic yelonehritis, ureteral reflux, renal artery stenosis and other causes of glomeruloathies [14,17]. Today, atients without any of the above conditions may be considered for NSS, since cancer secific survival and metastasis free survival are similar in all T1N0M0 renal tumors treated with NSS or radical nehrectomy [18-21]. Furthermore, NSS is associated with a decreased risk of chronic kidney disease, cardiovascular events and mortality when comared to radical nehrectomy [10]. Oen NSS can be by far more comlex than radical nehrectomy. Several decades ago, reorts on oen NSS described a greater risk of comlications including: acute

4 Palacios et al. BMC Research Notes 2013, 6:399 Page 4 of 5 Table 3 Comlications associated with NSS Comlications Urologic Excessive blood loss with transfusion Arista Prolonged urinary leak 1 ~ >25% reduction in GFR Other^ N/A Non-urologic Ileus Wound infection N/A Other * 3 ~ ~, one atient had two comlications (readmission within 30 days for chest ain with a negative evaluation and rolonged urinary drainage-drain removed on POD#10. ^, acute renal failure resulting in any dialysis, ureteral obstruction or kidney loss. *, cardiac, gastrointestinal ulmonary, thromboembolic, incisional or other. N/A, not alicable. renal failure, urinary fistula, hemorrhage and others [14,22]. For examle, Cambell et al. described comlication rates after oen NSS of 37% for symtomatic tumors and of 22% for incidental tumors [14]. Comlication rates associated with NSS (e.g., overall morbidity rate, hosital stay, blood losses, and frequency of acute renal failure) have decreased significantly [23,24], which may be attributed to the greater exerience of the urologist [25] or erhas due to the incororation of various new technologies (i.e., hemostatic agents, lasers, etc.) into the rocedure. Interestingly, the use of NSS has increased only by 20% from 1995 to 2007 with 72% of Medicare beneficiaries with localized tumors being managed with radical nehrectomy [26]. With the comarable survival rates and decreasing morbidities, it is unclear why NSS remains underutilized in this oulation. In our small, we were able to comare the use of and Arista W in this. Increased risk of bleeding was not evident with the use of the new haemostatic agent, Arista W. Haemostatic agents such as or Arista W in addition with an adequate surgical technique were adequate in maintaining ost-oerative haemostasis. No atient was noted to have a clinical ost-oerative bleed. Several benefits exist with Arista W. First, no mixing is required and thus the agent can be used immediately. Second, Arista W is a synthetic haemostatic reagent and is made from human lasma, the latter may carry a risk for virus or rion infection. This is the first reort of Arista W being used in a NSS. Radiologic imaging after comlex renal surgery may be roblematic and thus urologist may have to clearly describe surgical technique to the radiologist interreting ost-oerative scans. For examle, we noticed on several occasions Surgicel W ledgets have a sace occuying low attenuation aearance, which could mimic an abscess (Figure 1). Thus we must stress that in the immediate ost-oerative setting (i.e., with 30 days), unless the atient has fever, elevated white blood cells count that caution must be exercised in over interreting ost-oerative imaging. Our study has several limitations. First, it is a small retrosective study from a single center erformed by one surgeon. Next, our follow-u was limited (mean follow-u of 18 months) to reliably reort any differences in oncologic outcomes. This short follow-u, however, is sufficient when assessing intra-oerative and ost-oerative outcomes. Lastly, we devoted significant attention to the cut surface of the kidney (i.e., tying off lobar vessels, coagulating renal cortex with Argon laser in addition to lacing a Figure 1 Pre-oerative and ost-oerative CT scan of atient who underwent NSS. A) Pre-oerative CT scan with intravenous contrast demonstrated 4 cm solid, exohytic mass in the lower ole of the left kidney. Patient underwent an oen left NSS. B) Four weeks after NSS, atient resented to Emergency Deartment (ED) with abdominal ain. Patient was without fever/chills, elevated white blood cell count or an abnormal urinalysis. However, CT scan in the ED was interruted as an abscess at the surgical site in the left kidney. Arrow illustrating fluid collection. C) Due to the unimressive clinical scenario, no intervention was erformed and a reeat CT scan of the abdomen 8 weeks after the visit to the ED noted healing surgical site. Arrow illustrating reduction in fluid collection and healing arenchyma.

5 Palacios et al. BMC Research Notes 2013, 6:399 Page 5 of 5 Surgicel W ledget). Thus the true need for the haemostatic agent cannot be answered in this study. Conclusion In conclusion, along with meticulous surgical technique, the use of either haemostatic agent ( or Arista W ) was not associated with high rate of intra-oerative or ost-oerative haemorrhage. When requiring the alication of a haemostatic agent during NSS, either haemostatic agent studied may be successfully emloyed. Abbreviations CT: Comuted tomograhy; MRI: Magnetic resonance imaging; GFR: Glomerular filtration rate; RCC: Renal cell carcinoma; NSS: Nehron saring surgery; BMI: Body mass index. Cometing interests The authors declare that they have no cometing interests. Authors contributions DAP, MD - Study concet and design, drafting of manuscrit. MMc, MD Study concet and design, drafting of manuscrit. MM, MD, PhD Statistical analysis and drafting of manuscrit. CJR, MD, MBA - Study concet and design, drafting of manuscrit. All authors have read and aroved the final manuscrit. Author details 1 Section of Urologic Oncology, MD Anderson Cancer Center Orlando, Orlando, FL 32806, USA. 2 Deartment of Urology, Celebration Hosital Florida Hosital, Celebration, FL 34747, USA. 3 Cancer Research Institute, Orlando Health, 6900 Lake Nona Blvd, Orlando, FL 32527, USA. Received: 17 Aril 2013 Acceted: 24 Setember 2013 Published: 3 October 2013 References 1. Siegel R, Naishadham D, Jemal A: Cancer statistics, CA Cancer J Clin 2012, 62: Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr: Rising incidence of renal cell cancer in the United States. JAMA 1999, 281: Rini BI, Cambell SC, Escudier B: Renalcellcarcinoma.Lancet 2009, 373: Bluth EI, Bush WH Jr, Amis ES Jr, et al: Indeterminate renal masses: American college of radiology. ACR aroriateness criteria. Radiology 2000, 215: Patard JJ, Kim HL, Lam JS, Dorey FJ, Pantuck AJ, Zisman A, Ficarra V, Han KR, Cindolo L, De La Taille A, Tostain J, Artibani W, Dinney CP, Wood CG, Swanson DA, Abbou CC, Lobel B, Mulders PF, Choin DK, Figlin RA, Belldegrun AS: Use of the university of California Los Angeles integrated staging system to redict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol 2004, 22: Molina AM, Motzer RJ: Clinical ractice guidelines for the treatment of metastatic renal cell carcinoma: today and tomorrow. Oncologist 2011, 16: Robson CJ, Churchill BM, Anderson W: The results of radical nehrectomy for renal cell carcinoma. J Urol 1969, 101: Robey EL, Schellhammer PF: The adrenal gland and renal cell carcinoma: is isilateral adrenalectomy a necessary comonent of radical nehrectomy? J Urol 1986, 135: Novick AC, Streem S, Montie JE, Pontes JE, Siegel S, Montague DK, Goormastic M: Conservative surgery for renal cell carcinoma: a single-center exerience with 100 atients. J Urol 1989, 141: Huang WC, Elkin EB, Levey AS, et al: Partial nehrectomy versus radical nehrectomy in atients with small renal tumors is there a difference in mortality and cardiovascular outcomes? J Urol 2009, 181: FLOSEAL: Hemostatic Matrix Instructions For Use. Hayward, CA: Baxter Healthcare Cororation; 2010: Oz MC, Cosgrove DM 3rd, Badduke BR, et al: Controlled clinical trial of a novel hemostatic agent in cardiac surgery. Ann Thorac Surg 2000, 69: Matsushita T, Masuda S, Inoue T: Early exerience with combined use of two lant-based hemostatic agents. Ann Thorac Surg 2010, 90: Cambell SC, Novick AC, Streem SB, Klein E, Licht M: Comlications of nehron saring surgery for renal tumors. J Urol 1994, 151: Reifsnyder JE, Ramasamy R, Ng CK, Diietro J, Shin B, Shariat SF, Del Pizzo JJ, Scherr DS: Laaroscoic and oen artial nehrectomy: comlication comarison using the Clavien system. JSLS 2012, 16: Gill IS, Kavoussi LR, Lane BR, Blute ML, Babineau D, Colombo JR Jr, Frank I, Permongkosol S, Weight CJ, Kaouk JH, Kattan MW, Novick AC: Comarison of 1,800 laaroscoic and oen artial nehrectomies for single renal tumors. J Urol 2007, 178: Uzzo R, Novick A: Nehron saring surgery for renal tumors: indications. Techniques and outcomes. J Urol 2001, 166: Créel M, Jeldres C, Perrotte P, et al: Nehron-saring surgery is equally effective to radical nehrectomy for t1bn0m0 renal cell carcinoma: a oulation-based assessment. Urology 2010, 75: Thomson R, Siddiqui S, Lohse C, et al: Partial versus radical nehrectomy for 4 to 7 cm renal cortical tumors. J Urol 2009, 182: Pahernik S, Roos F, Röhrig B, et al: Elective nehron saring surgery for renal cell carcinoma larger than 4 cm. J Urol 2008, 179: Van Poel H, Pozzo L, Albrecht W, et al: A rosective, randomised eortc intergrou hase 3 study comaring the oncologic outcome of elective nehron-saring surgery and radical nehrectomy for low-stage renal cell carcinoma. Eur Urol 2011, 59: Duque JL, Loughlin KR, O Leary MP, Kumar S, Richie JP: Partial nehrectomy: alternative treatment for selected atients with renal cell carcinoma. Urology 1998, 52: Corman JM, Penson DF, Hur K, Khuri SF, Daley J, Henderson W, Krieger JN: Comarison of comlications after radical and artial nehrectomy: results from the National Veterans Administration Surgical Quality Imrovement Program. BJU Int 2000, 86: Shekarriz B, Uadhyay J, Shekarriz H, de Assis Mendes Goes F Jr, Bianco FJ, Tiguert R, Gheiler E, Wood DP Jr: Comarison of costs and comlications of radical and artial nehrectomy for treatment of localized renal cell carcinoma. Urology 2002, 59: Dall Oglio MF, Ballarotti L, Passerotti CC, Paluello DV, Colombo JR Jr, Cria A, Srougi M: Anatrohic nehrotomy as nehron-saring aroach for comlete removal of intraarenchymal renal tumors. Int Braz J Urol 2012, 38: Smaldone MC, Kutikov A, Egleston B, et al: Assessing erformance trends in laaroscoic nehrectomy and nehron saring surgery for localized renal tumors. Urology 2012, 80: doi: / Cite this article as: Palacios et al.: Pilot study comaring the two hemostatic agents in atients undergoing artial nehrectomy. BMC Research Notes :399. Submit your next manuscrit to BioMed Central and take full advantage of: Convenient online submission Thorough eer review No sace constraints or color figure charges Immediate ublication on accetance Inclusion in PubMed, CAS, Scous and Google Scholar Research which is freely available for redistribution Submit your manuscrit at