A Review of Current Hemostatic Agents and Tissue Sealants Used in Laparoscopic Partial Nephrectomy

Treatment Review

4_RIU0524_09-30.qxd 9/29/11 7:52 PM Page 131 TREATMENT REVIEW A Review of Current Hemostatic Agents and Tissue Sealants Used in Laparoscopic Partial Nephrectomy I. Galanakis, MD, FEBU, N. Vasdev, MD, MRCS, N. Soomro, MD, FRCS Department of Urology, Freeman Hospital, Newcastle upon Tyne, United Kingdom Laparoscopic partial nephrectomy (LPN) is currently considered to be one of the most challenging procedures in minimally invasive urological surgery. With an increasing number of renal tumors being managed using LPN, there is now a further interest in the development of techniques and agents to reduce complications associated with the procedure. Hemostasis is of paramount importance during LPN, and hemostatic agents and tissue sealants are now being used commonly during LPN. Despite this, there is a dearth of prospective, randomized, human trials in current literature that compare the various agents. This review evaluates hemostatic agents and tissue sealants being used during LPN as an adjuvant to suturing in human studies. [Rev Urol. 2011;13(3):131-138 doi: 10.3909/riu0524] © 2011 MedReviews®, LLC Key words: Laparoscopic partial nephrectomy • Renal tumors • Hemostatic agents • Tissue sealants • Suturing adjuvant he first laparoscopic nephrectomy was performed by Clayman and colleagues in 1991 and is now recognized as a major landmark in urology.1 Following this procedure, there has been a gradual global rise in minimally invasive urological surgery (MIUS) that has led to a rapid increase in research and techniques within this field. In Europe and the United States, the use of robotic systems is currently revolutionizing MIUS and it is now envisaged that only a few open techniques will be reserved for select cases. Laparoscopic partial nephrectomy (LPN) is considered to be one of the most technically challenging types of MIUS, with a steep learning curve and potential for complications.2 With regard to postoperative hemorrhage, a large multiinstitutional, retrospective study was conducted by Gill and colleagues, who T VOL. 13 NO. 3 2011 REVIEWS IN UROLOGY 131 4_RIU0524_09-30.qxd 9/29/11 7:52 PM Page 132 Hemostatic Agents and Tissue Sealants Used in LPN continued compared the outcomes of 1028 and 771 patients undergoing open partial nephrectomy (OPN) and LPN, respectively. Hemorrhage was found in 1.6% and 4.2% of these patients, respectively (P  .0002), despite the fact that the open procedures had been reserved for larger and more centrally located tumors.3 Minimizing blood loss in the operating field is a key factor during LPN as even the smallest amount of bleeding can compromise vision during laparoscopy due to light absorption by blood. More importantly, a poor view associated with hemorrhage can affect the outcome during suturing repair. To maximize hemostasis following the excision of the tumor and to reduce the rate of postoperative hemorrhagic events, a wide variety of hemostatic tools have been transferred from open surgery or developed specifically for use during LPN. This review describes the currently available hemostatic and sealing agents used to achieve parenchymal hemostasis during LPN that have (approximately 30) that produce fibrin to form a stable hemostatic plug. The aim of all hemostatic agents is to act by imitating, promoting, or bypassing specific steps of the coagulation cascade. The aim of all hemostatic agents is to act by imitating, promoting, or bypassing specific steps of the coagulation cascade. Fibrin Sealants or Glues The idea of promoting hemostasis using fibrin was first reported by Bergel in 1909.4 Fibrin sealants, as we know them today, have been commercially available in Europe and Japan for over 30 years with a good safety profile.5 However, it was not until 1998 that the US Food and Drug Administration (FDA) approved their use due to concerns over the transmission of infectious disease as these products were developed from pooled plasma components.6 Fibrin sealants are designed to mimic the final steps of the blood coagulation cascade, forming a stable, To maximize hemostasis following the excision of the tumor and to reduce the rate of postoperative hemorrhagic events, a wide variety of hemostatic tools have been transferred from open surgery or developed specifically for use during LPN. been evaluated in human LPN trials (Table 1) and also discusses agents being evaluated in animal LPN studies (Table 2). Hemostasis Hemostasis is a rather complex process. The injury of a blood vessel triggers the following sequence: (1) vessel constriction to reduce blood flow; (2) adherence of circulating platelets to the vessel wall at the site of the trauma; and (3) platelet activation and aggregation, coupled with an intricate series of enzymatic reactions involving coagulation proteins 132 VOL. 13 NO. 3 2011 plastic, oral, and maxillofacial surgery.9 However, more and more urologic applications are being reported. The use of fibrin sealants in renal injuries or OPN has been evaluated with good immediate and physiologic fibrin clot that assists hemostasis and wound healing. These agents work best in a dry surgical field. Fibrin sealants essentially contain human fibrinogen and humanor bovine-derived thrombin. Further components include antifibrinolytic agent (eg, aprotinin), calcium chloride, and factor XIII.7 They can be manufactured from pooled blood or single-source donors or can be made specifically from the patient’s own blood.7,8 Fibrin glues have initially been used in a variety of settings including cardiac, vascular, reconstructive REVIEWS IN UROLOGY long-term results.10,11 With regard to LPN, Pruthi and colleagues were the first to report their experience with the use of TISSEEL (Baxter Healthcare Corporation, Westlake Village, CA), in 15 patients undergoing hand-assisted LPN for renal tumor (mean size, 2.7 cm).12 In all cases, electrocauterization and argon-beam coagulation followed by the application of TISSEEL was successful in obtaining strict hemostasis of the surgical bed, with no evidence of acute or delayed hemorrhage.12 On the other hand, Johnston and colleagues reported that the use of fibrin glues may offer adequate hemostasis in patients undergoing LPN when the collecting system or renal sinus is not entered, but in case of entering, a sutured bolster is recommended.13 In support, a recent, randomized animal study, which compared various tissue sealants (FLOSEAL Hemostatic Matrix, Baxter Healthcare; Quixil® Solutions for Sealant, Ethicon, Somerville, NJ; TISSUCOL, Baxter Healthcare) with conventional suturing during LPN, emphasized the need for suturing in cases where the urinary tract opened.14 Nevertheless, in 2007, Porpiglia and coworkers published results to the contrary. They prospectively compared two groups of patients, similar in baseline characteristics, undergoing LPN: group A (n  24) received parenchymal suture, whereas group B (n  20) received parenchymal suture with fibrin glue (TISSUCOL) and collagen fleece (TissuFleece E; VOL. 13 NO. 3 2011 REVIEWS IN UROLOGY Activates the conversion of fibrinogen to fibrin TachoSil® (Nycomed) LPN, laparoscopic partial nephrectomy. Human fibrinogen and thrombin fleece Glutaraldehyde crosslinks bovine albumin to cell proteins at wound site to form a strong adhesive BioGlue® (Cryolife) Provides matrix for clotting initiation SURGICEL®/ TABOTAMP (Ethicon), Oxycel® (Becton Dickinson) Oxidized regenerated methylcellulose Glutaraldehydebased adhesives Provides a matrix for clot formation and activates autologous thrombin Vivostat® (Vivostat A/S) FloSeal (Baxter Healthcare), SURGIFLO® (Ethicon) Idem TISSEEL/TISSUCOL (Baxter Healthcare), Hemaseel® HMN (Haemacure Corp.) EVISEL®/Quixil® (Ethicon) Fibrin glues Gelatin-based sealant Activates the conversion of fibrinogen to fibrin Product Category Mechanism of Action Human No No Autologous Autologous Human Fibrinogen Human No No Human Autologous Human Thrombin Human, pooled Bovine albumin Synthetic Human, pooled Autologous plasma Human, pooled Source Table 1 Hemostatic and Sealing Agents Currently Used in LPN and Evaluated in Human LPN Studies No need for preparation or reconstitution Use even in bleeding disorders Rather difficult to apply laparoscopically Rapid polymerization No suture after solidification Dry field preferred Bovine product Quite expensive Ease of use Low pH: (i) antimicrobial effect, (ii) not used with biologic agents (thrombin), (iii) may increase surrounding tissue inflammation Contains bovine products Surgiflo porcine gelatin Requires blood in the field Not a sealing agent Dry field Sequential application Autologous only source Dry field Sequential application Requires thawing. Spray delivery system for Tisseel (DUPLOSPRAY MIS) Possible allergic reactions Hemaseel HMN is expected No aprotinin in EVICEL Comments 33-36 42, 43 13, 39, 40 24-30, 44, 45 17,18 12, 13, 15, 17, 18, 44, 45, 52 References 4_RIU0524_09-30.qxd 9/29/11 7:52 PM Page 133 Hemostatic Agents and Tissue Sealants Used in LPN 133 4_RIU0524_09-30.qxd 9/29/11 7:52 PM Page 134 Hemostatic Agents and Tissue Sealants Used in LPN continued Table 2 Hemostatic and Sealing Agents Evaluated as Adjuncts During LPN and Evaluated Only in Animal LPN Studies Category Mechanism of Action Source Comments References Fibrin glue Activates the conversion of fibrinogen to fibrin Bovine collagen and Dry field thrombin  patient-derived No aprotinin fibrinogen Viral infections 46, 47 Hemostatic fibrin sealant powder Mixture of lyophilized human fibrinogen and thrombin prepared as a fine powder; when activated by exposure to moisture, it immediately forms a dense fibrin clot Human Ease of use Uniform application Lack of preparation time Not yet commercially available Good results 48 Polyethylene glycol hydrogel Two synthetic polyethylene glycol polymers that mix and crosslink in wound site Synthetic Does not require 47, 49 patient’s blood Is not exothermic, does not cause inflammation or infection Contradictory results in studies Expensive Cyanoacrylates Liquid monomers form polymers in the presence of water and in turn a cyanoacrylate bridge, binding the wound edges together Synthetic Rapid polymerization Dry field preferred Useful but only as an additive Glubran use is reported in humans,40 no data available 50 Granulated mineral Nonwoven gauze impregnated with kaolin that absorbs the smaller water granules, leaving the larger clotting factors and platelets in the wound Synthetic Efficacy also in sealing in a single, small study Ease of use and inexpensive Exothermic Dry field 51 LPN, laparoscopic partial nephrectomy. Baxter Healthcare).15 The authors concluded that the suturing was the key component for hemostasis in patients undergoing LPN and sealants did not influence their results significantly.15 An important landmark in the field of hemostatic agents was the development of CROSSEAL (Ethicon) in 2003. This fibrin sealant was manufactured entirely from nonanimal components and lacked, therefore, the bovine aprotinin and, as a consequence, avoided the potential allergic reactions or prion infections associated with bovine products.16 CROSSEAL was replaced in 2006 by Evicel® Fibrin Sealant (Ethicon). This was an identical 134 VOL. 13 NO. 3 2011 sealant except it lacked the tranexamic acid (a fibrin clot stabilizer) that has been associated with neurologic complications.7 Vivostat® (Vivostat A/S, Alleroed, Denmark) is an autologous, plateletenriched, fibrin sealant applicator system that utilizes 120 mL of the patient’s blood, which is processed overnight. Schips and colleagues published their results with 10 patients undergoing LPN (mean tumor size, 2.7 cm).17 After tumor excision and placement of two sutures, Vivostat was applied and there was no acute or delayed hemorrhage. Likewise, Gidaro and colleagues have recently reported REVIEWS IN UROLOGY similar results with 28 patients undergoing LPN (mean tumor size, 2.5 cm), although they also applied suture and bolster in 67% and 80% of patients, respectively.18 There is much research ongoing in the development of newer fibrin sealants for application during LPN and, despite the fact that many preliminary animal studies are favorable, outcomes in human patients and in large series need to be evaluated. Gelatin-Based Sealants The first gelatin-based sealant (Gelfoam®, Baxter Healthcare)) was used in 1945. A further revolution in 4_RIU0524_09-30.qxd 9/29/11 7:52 PM Page 135 Hemostatic Agents and Tissue Sealants Used in LPN this field was the introduction of FloSeal in 1999.19 The FloSeal Matrix consists of a bovine-derived gelatin matrix component with a calcium chloride solution and a humanderived thrombin component.20 When FloSeal is applied to the bleeding surface, its granules allow high concentrations of thrombin to react rapidly with the patient’s fibrinogen and form a mechanically stable fibrin clot. As blood percolates through the gelatin matrix, the granules swell approximately 20% within 10 minutes, reducing blood flow and providing gentle tamponade, conforming to the wound’s shape. The clot is reabsorbed after 6 to 8 weeks.20,21 The unique characteristic of FloSeal is the requirement for the presence of blood at its application site for activation. As with fibrin sealants, there is a treatment risk of developing bovine spongiform encephalitis or IgEmediated anaphylaxis.22,23 Moreover, injection of FloSeal directly into medium to large vessels can theoretically cause thromboembolic events.23 The use of FloSeal for urologic surgery has been mainly in trauma and partial nephrectomy (laparoscopic or open) where it has been assessed on animal models and case series. With regard to LPN, the first report of using FloSeal as an adjunct, efficacious haemostatic agent was made by User and Nadler.24 Richter and colleagues reported their use of FloSeal in a case series of 25 patients undergoing partial nephrectomy (15 OPN, 10 LPN) for small renal tumors (mean size, 2.8 cm). In this series, FloSeal provided immediate and durable hemostasis, without the need for suturing.25 Gill and coworkers published a prospective study comparing 63 patients undergoing LPN using FloSeal with 68 patients undergoing LPN without the use of FloSeal.26 The results showed that the adjunctive use of FloSeal substantially enhanced parenchymal hemostasis and reduced postoperative hemorrhagic complications to levels comparable with previous contemporary OPN series.26 Further studies reported similar positive results.27,28 Weld and colleagues published their experience for the first 60 LPN cases performed by a single surgeon.29 In this series, the authors described using both FloSeal and fibrin glue but later stopped using the fibrin glue. The interesting outcome of this series was that, despite the exclusion of fibrin glue in the more recent cases, there was no clinical or statistical difference in the incidence of bleeding or leakage.29 SURGIFLO® (an evolution of SURGIFOAM®; Ethicon) is another currently used gelatin matrix thrombin sealant, though of porcine origin. This agent can also be mixed with sterile saline instead of thrombin. Nogueira and colleagues prospectively compared SURGIFLO with FloSeal in 35 patients undergoing LPN by a single surgeon and reported no notable differences in terms of hemostasis, handling, or ease of application.30 Accessibility, ease of use, and effective hemostasis make FloSeal a popular tool in reducing surgical morbidity from blood loss in patients undergoing a LPN. lacks the bovine aprotinin. Upon contact with blood or other fluids, the coagulation factors react to form a fibrin clot that sticks TachoSil to the tissue surface, producing an air- and liquid-tight seal in 3 to 5 minutes. It is biodegradable and may be applied directly to the bleeding surface without the need for preparation or reconstitution. Rassweiler and colleagues reported their positive experience with the use of TachoComb in LPN.33 An interesting prospective, randomized, multicenter study was published later by Siemer and colleagues, although it studied use in OPN.34 The authors compared TachoSil with standard suturing in 185 patients undergoing OPN for small renal tumors and concluded it was superior to standard suturing in obtaining intraoperative control of hemorrhage and equally well tolerated. Hacker and coworkers used TachoComb and fibrin glue as preventive measures for delayed bleeding in 25 LPN cases.35 Falsaperla and associates recently reported their experience with the use of TachoSil in 14 patients who underwent LPN for small peripheral tumors (mean size, 3.4 cm).36 After suturing the parenchyma, they applied TachoSil directly on the bloody surface of the tumoral bed and found no immediate or delayed hemorrhage or other complications in any of the patients. Human Fibrinogen and Thrombin Fleece TachoSil® (Nycomed, Zurich, Switzerland) is a sterile, ready-to-use absorbable patch for intraoperative topical application. It consists of an equine-collagen sponge coated with the human coagulation factors fibrinogen and thrombin.31 It was launched in 2004 but only approved by the FDA in April 2010.32 It is the evolution of TachoComb® (Nycomed), as it now contains a purely human coagulation factor component and Oxidized Regenerated Methylcellulose Oxidized cellulose was first introduced in 1942 by Frantz, after which SURGICEL® (Ethicon) was launched into the clinical market in 1960.37 SURGICEL is a plant-based topical hemostatic made by regenerating pure plant-derived cellulose into a knitted fabric that is then oxidized.38 When it is applied topically, it absorbs blood and becomes a gel covering the site of vessel injury. Contact with moisture triggers the breakdown of cellulose and the release of cellulosic VOL. 13 NO. 3 2011 REVIEWS IN UROLOGY 135 4_RIU0524_09-30.qxd 9/29/11 7:52 PM Page 136 Hemostatic Agents and Tissue Sealants Used in LPN continued acid that lowers the topical pH. That causes localized vasoconstriction but also provides bactericidal properties. However, SURGICEL’s main hemostatic effect is achieved by providing a matrix for platelet adhesion, accelerating the creation of the platelet plug that will form the foundation of the fibrin clot.37,38 SURGICEL is currently widely used in LPN, not only for controlling mild bleeding but also in the form of “surgical bolster.” Following the excision of the tumor, SURGICEL is positioned within a sutured bolster into the defect, achieving approximation and local compression at the resected site, as in the open technique.13,39 In a multi-institutional survey from Europe and the United States (18 centers with 1347 LPN cases), parenchymal suturing over bolster of SURGICEL was consistently used by 16 centers.40 Of the remaining two, one center (50 cases) never performed suturing/ bolstering, using only sealants, and the other (35 cases) reported variable use of a bolster suture and/or central hemostatic suture depending on the depth of the lesion. Glutaraldehyde-Based Adhesive BioGlue® (CryoLife, Kennesaw, GA) was first released in Europe in 1998. It is a two-component surgical adhesive composed of solutions of purified bovine serum albumin (BSA) and glutaraldehyde.41 The glutaraldehyde molecules covalently bond (crosslink) the BSA molecules to each other and on application to the tissue proteins at the repair site, creating a flexible mechanical seal independent of the body’s clotting cascade. BioGlue begins to polymerize within 20 to 30 seconds and reaches its bonding strength within approximately 2 minutes.41 Nadler and colleagues were the first to report their positive experience with the use of BioGlue in 8 LPN cases (mean tumor size, 2.8 cm), both 136 VOL. 13 NO. 3 2011 as a hemostatic and as a protective covering over the tumor resection site.42 Nevertheless, they underlined some interesting technical points, such as the dry surgical field as a prerequisite for the successful adherence of BioGlue to the application site, the risk of hardening within the collecting system, and the extreme difficulty of placing sutures after it has solidified.42 In a larger study, Hidas and colleagues retrospectively compared 143 patients who underwent traditional sutured OPN with 31 patients undergoing a sutureless BioGlue sealing-only procedure. Despite the retrospective nature of the study, the patient and tumor characteristics were similar in both groups. The authors concluded that BioGlue alone provided adequate hemostasis during nephron-sparing surgery, and significantly decreased blood loss and the laparoscopically. Technical modifications and refinements, as well as a number of hemostatic tools, have been added to the armamentarium of urologic surgeons. In particular, hemostatic agents and sealants, with over 100 years of history, play an important role. In a recent multiinstitutional LPN study, over 80% of urologists used sealants as an adjunct.39 Choice is variable from one surgeon to another and may depend on individual experience rather than a strong evidence base. It is obvious that useful recommendations cannot be made because of the lack of properly designed, prospective, randomized human trials. Nevertheless, by no means should the use of hemostatic agents preclude proper laparoscopic suturing with surgical bolsters. There may be examples of small peripheral tumors By no means should the use of hemostatic agents preclude proper laparoscopic suturing with surgical bolsters. transfusion rate, as well as the renal ischemic and operative times.43 Other Agents A great number of hemostatic and sealing agents are currently in use in all surgical specialties and research is ongoing. Not all of them are, naturally, suitable for LPN. Table 2 briefly presents the agents that have been evaluated in LPN-only trials. Conclusions OPN is currently considered the gold standard for the treatment of small renal cancers. However, the need for less morbidity without compromising the oncological and surgical outcome is directing urologists toward LPN. Centers of excellence have shown that duplication of established open surgical principles is possible REVIEWS IN UROLOGY that can be treated with the complementary use of sealants and bipolar coagulation, but in case of a bigger tumor, when ischemia is required, sutures with bolster are essential. Interestingly, there are authors proposing that, in the future, to determine a standard hemostasis technique, rather than relying on the development of sealants, we should rely on innovations in suture techniques.15 The search for the ideal efficient hemostatic agent continues. Until that day, the urologic surgeon should have a detailed knowledge of the available agents and must be sure that by using them he will have better results than with those using standard methods. Most importantly, he must keep in mind that hemostatic agents and tissue sealants should not be considered as a surgical alternative 4_RIU0524_09-30.qxd 9/29/11 7:52 PM Page 137 Hemostatic Agents and Tissue Sealants Used in LPN technique, but rather as an adjunct to facilitate and achieve the optimal surgical outcome. 15. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Clayman RV, Kavoussi LR, Soper NJ, et al. Laparoscopic nephrectomy: initial case report. J Urol. 1991;146:278-282. Ramani AP, Desai MM, Steinberg AP, et al. Complications of laparoscopic partial nephrectomy in 200 cases. J Urol. 2005;173:42-47. Gill IS, Kavoussi LR, Lane BR, et al. Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol. 2007;178:41-46. Bergel S. Ueber wirkungen des fibrins. Dtsch Med Wochenschr. 1909;35:663-665. Urlesberger H, Rauchenwald K, Henning K. Fibrin adhesives in surgery of the renal parenchyma. Eur Urol. 1979;5:260-261. Jackson MR. Fibrin sealants in surgical practice: an overview. Am J Surg. 2001;182(2 suppl): 1S-7S. Ramanathan R, Leveillee RJ. A review of methods for hemostasis and renorrhaphy after laparoscopic and robot-assisted laparoscopic partial nephrectomy. Curr Urol Rep. 2010;11: 208-220. Msezane LP, Katz MH, Gofrit ON, et al. Hemostatic agents and instruments in laparoscopic renal surgery. J Endourol. 2008;22:403-408. Sundaram CP, Keenan AC. Evolution of hemostatic agents in surgical practice. Indian J Urol. 2010;26:374-378. Kram HB, Ocampo HP, Yamaguchi MP, et al. Fibrin glue in renal and ureteral trauma. Urology. 1989;33:215-218. Levinson AK, Swanson DA, Johnson DE, et al. Fibrin glue for partial nephrectomy. Urology. 1991;38:314-316. Pruthi RS, Chun J, Richman M. The use of a fibrin tissue sealant during laparoscopic partial nephrectomy. BJU Int. 2004;93:813-817. Johnston WK 3rd, Montgomery JS, Seifman BD, et al. Fibrin glue v sutured bolster: lessons learned during 100 laparoscopic partial nephrectomies. J Urol. 2005;174:47-52. Rouach Y, Delongchamps NB, Patey N, et al. Suture or hemostatic agent during laparoscopic 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. partial nephrectomy? A randomized study using a hypertensive porcine model. Urology. 2009;73:172-177. Porpiglia F, Renard J, Billia M, et al. Biological glues and collagen fleece for hemostasis during laparoscopic partial nephrectomy: technique and results of prospective study. J Endourol. 2007;21:423-428. Schexneider KI. Fibrin sealants in surgical or traumatic hemorrhage. Curr Opin Hematol. 2004;11:323-326. Schips L, Dalpiaz O, Cestari A, et al. Autologous fibrin glue using the Vivostat system for hemostasis in laparoscopic partial nephrectomy. Eur Urol. 2006;50:801-805. Gidaro S, Cindolo L, Lipsky K, et al. Efficacy and safety of the haemostasis achieved by Vivostat system during laparoscopic partial nephrectomy. Arch Ital Urol Androl. 2009;81: 223-227. FloSeal™ Matrix. FDA Approval Letter. December 8, 1999. Floseal™ Hemostatic Matrix Instructions For Use. Hayward, CA: Baxter Healthcare Corporation; 0710217 May 2010. Oz MC, Rondinone JF, Shargill NS. FloSeal Matrix: new generation topical hemostatic sealant. J Card Surg. 2003;18:486-493. Martinowitz U, Saltz R. Fibrin sealant. Curr Opin Hematol. 1996;3:395-402. Shekarriz B, Stoller ML. The use of fibrin sealant in urology. J Urol. 2002;167:1218-1225. User HM, Nadler RB. Applications of FloSeal in nephron-sparing surgery. Urology. 2003;62: 342-343. Richter F, Schnorr D, Deger S, et al. Improvement of hemostasis in open and laparoscopically performed partial nephrectomy using a gelatin matrix-thrombin tissue sealant (FloSeal). Urology. 2003;61:73-77. Gill IS, Ramani AP, Spaliviero M, et al. Improved hemostasis during laparoscopic partial nephrectomy using gelatin matrix thrombin sealant. Urology. 2005;65:463-466. Weight CJ, Lane BR, Gill IS. Laparoscopic partial nephrectomy for selected central tumors: omitting the bolster. BJU Int. 2007;100:375-378. Wille AH, Johannsen M, Miller K, Deger S. Laparoscopic partial nephrectomy using FloSeal for hemostasis: technique and experiences in 102 patients. Surg Innov. 2009;16:306-312. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. Weld KJ, Venkatesh R, Huang J, Landman J. Evolution of surgical technique and patient outcomes for laparoscopic partial nephrectomy. Urology. 2006;67:502-506; discussion 506-507. Nogueira L, Katz D, Pinochet R, et al. Comparison of gelatine matrix-thrombin sealants used during laparoscopic partial nephrectomy. BJU Int. 2008;102:1670-1674. TachoSil [package insert]. Zurich: Nycomed Gmbh; 2010. TachoSil®. FDA Approval Letter. April 2, 2010. Rassweiler JJ, Abbou C, Janetschek G, Jeschke K. Laparoscopic partial nephrectomy. The European experience. Urol Clin North Am. 2000;27:721736. Siemer S, Lahme S, Altziebler S, et al. Efficacy and safety of TachoSil as haemostatic treatment versus standard suturing in kidney tumor resection: a randomised prospective study. Eur Urol. 2007;52:1156-1163. Häcker A, Albadour A, Jauker W, et al. Nephron-sparing surgery for renal tumours: acceleration and facilitation of the laparoscopic technique. Eur Urol. 2007;51:358-365. Falsaperla M, Autorino R, Puglisi M, et al. Haemostatic agents during laparoscopic nephron-sparing surgery: what about TachoSil? BJU Int. 2009;104:270-271. Achneck HE, Sileshi B, Jamiolkowski RM, et al. A comprehensive review of topical hemostatic agents: efficacy and recommendations for use. Ann Surg. 2010;251:217-228. Hong YM, Loughlin KR. The use of hemostatic agents and sealants in urology. J Urol. 2006;176: 2367-2374. Gill IS, Desai MM, Kaouk JH, et al. Laparoscopic partial nephrectomy for renal tumor: duplicating open surgical techniques. J Urol. 2002;167:469476; discussion 475-476. Breda A, Stepanian SV, Lam JS, et al. Use of haemostatic agents and glues during laparoscopic partial nephrectomy: a multiinstitutional survey from the United States and Europe of 1347 cases. Eur Urol. 2007;52: 798-803. BioGlue® Surgical Adhesive Instructions For Use. Kennesaw, GA: CryoLife; L6312.007 June 2010. Nadler RB, Loeb S, Rubenstein RA, Vardi IY. Use of BioGlue in laparoscopic partial nephrectomy. Urology. 2006;68:416-418. Main Points • Fibrin sealants are designed to mimic the final steps of the blood coagulation cascade, forming a stable, physiologic fibrin clot that assists hemostasis and wound healing. These agents work best in a dry surgical field. Fibrin sealants essentially contain human fibrinogen and human- or bovine-derived thrombin. Further components include antifibrinolytic agent (eg, aprotinin), calcium chloride, and factor XIII. They can be manufactured from pooled blood or single-source donors or can be made in specifically from the patient’s own blood. • Fibrin glues have been used in a variety of settings including cardiac, vascular, reconstructive plastic, oral, and maxillofacial surgery. More and more urologic applications are being reported. The use of fibrin sealants in renal injuries or OPN has been evaluated with good immediate and long-term results. • Hemostatic agents and tissue sealants should not be considered as a surgical alternative technique, but rather as an adjunct to facilitate and achieve the optimal surgical outcome. VOL. 13 NO. 3 2011 REVIEWS IN UROLOGY 137 4_RIU0524_09-30.qxd 9/29/11 7:52 PM Page 138 Hemostatic Agents and Tissue Sealants Used in LPN continued 43. 44. 45. 46. 138 Hidas G, Kastin A, Mullerad M, et al. Sutureless nephron-sparing surgery: use of albumin glutaraldehyde tissue adhesive (BioGlue). Urology. 2006;67:697-700; discussion 700. Venkatesh R, Weld K, Ames CD, et al. Laparoscopic partial nephrectomy for renal masses: effect of tumor location. Urology. 2006;67:11691174; discussion 1174. Desai PJ, Andrews PE, Ferrigni RG, Castle EP. Laparoscopic partial nephrectomy at the Mayo Clinic Arizona: follow-up surveillance of positive margin disease. Urology. 2008;71:283-286. Turner AS, Parker D, Egbert B, et al. Evaluation of a novel hemostatic device in an ovine VOL. 13 NO. 3 2011 47. 48. 49. REVIEWS IN UROLOGY parenchymal organ bleeding model of normal and impaired hemostasis. J Biomed Mater Res. 2002;63:37-47. Johnston WK 3rd, Kelel KM, Hollenbeck BK, et al. Acute integrity of closure for partial nephrectomy: comparison of 7 agents in a hypertensive porcine model. J Urol. 2006;175: 2307-2311. Bishoff JT, Cornum RL, Perahia B, et al. Laparoscopic heminephrectomy using a new fibrin sealant powder. Urology. 2003;62: 1139-1143. Bernie JE, Ng J, Bargman V, et al. Evaluation of hydrogel tissue sealant in porcine laparoscopic 50. 51. 52. partial-nephrectomy model. J Endourol. 2005; 19:1122-1126. Huang SH, Chiu AW, Lin CH, et al. Efficacy of ultrasonic tissue dissector and tissue glue for laparoscopic partial nephrectomy in a porcine model. Int Surg. 2003;88:199-204. Margulis V, Matsumoto ED, Svatek R, et al. Application of novel hemostatic agent during laparoscopic partial nephrectomy. J Urol. 2005; 174:761-764. Pick DL, Kolla SB, Mucksavage P, et al. Sprayed fibrin sealant as the sole hemostatic agent for porcine laparoscopic partial nephrectomy. J Urol. 2011;185:291-297.