423

JOURNAL OF ENDOUROLOGYVolume 21, Number 4, April 2007© Mary Ann Liebert, Inc.DOI: 10.1089/end.2006.0265

Biological Glues and Collagen Fleece for Hemostasis during Laparoscopic Partial Nephrectomy:

Technique and Results of Prospective Study

FRANCESCO PORPIGLIA, M.D., JULIEN RENARD, M.D., MICHELE BILLIA, M.D., IVANO MORRA, M.D., CARLO TERRONE, M.D., and ROBERTO MARIO SCARPA, M.D.

ABSTRACT

Purpose: The aim of this prospective study was to evaluate the advantages or disadvantages of the use of fi-brin glue and collagen fleece during laparoscopic partial nephrectomy.

Patients and Methods: Two groups of patients were studied. Group A (n � 24) received parenchymal su-ture, whereas Group B (n � 20) received parenchymal suture with fibrin glue and collagen fleece. The twogroups were similar in baseline characteristics. We evaluated patient age, size of the lesion at CT, operativetime, ischemia time, and sealant technique in relation to blood loss, hospital stay, and hemorrhagic compli-cations.

Results: No significant difference was observed in perioperative parameters (P � 0.05). The mean size oflesion was 3.3 � 1.2 (range 1–8 cm) for group A and 3.0 � 1.3 (range 2–5 cm) for Group B. The mean oper-ative time was 116 � 26.6 minutes (range 90–220 minutes) for group A and 130 � 23.5 minutes (range 90–210minutes) for group B. The mean warm ischemia time was 28.8 � 5.7 minutes (range 18–60) minutes) and35.6 � 6.2 minutes (range 20–52 minutes), respectively. The mean blood loss was 178 � 34.5 mL (range 50–400ml) for group A and 219 � 44.6 mL (range 80–750 ml) for group B. The mean hospital stay was 5.9 � 1.2days (range 5-8 days) for group A and 6.3 � 2.1 days (range 5–9 days) for group B. Four and two postoper-ative hemorrhage complications were observed in groups A and B, respectively.

Conclusion: The use of fibrin glues and collagen fleece should be considered an adjuvant, as it does notpresent any substantial advantages, the suture being the key point in hemostasis control. We believe that inorder to improve hemostasis, the efficacy of other types of sealants should be studied, as we were not con-vinced by those we used.

INTRODUCTION

NOWADAYS, IN UROLOGIC CENTERS where advancedlaparoscopy is performed, laparoscopic nephron-sparing

surgery is frequently considered for the treatment of small re-nal tumors. With the constant evolution and refinement of thetechnique, initially indicated only for favorably located, small,peripheral, exophytic tumors,1–3 things have changed. Today,according to some authors,4,5 this approach can be consideredfor larger, deeper lesions even in solitary kidneys. Neverthe-less, procedure often is linked to a high rate of complications,

mostly involving hemorrhage and urinary leakage, impedingwider diffusion of the technique.6,7

In order to reduce the rate of postoperative hemorrhagicevents, different solutions have been proposed, ranging fromsimple parenchymal suture to the use of fibrin glue, collagenfleece, the argon-beam coagulator, and other hemostatic mea-sures. However, no procedure has yet been described nor ac-cepted as the standard for the prevention of hemorrhage duringlaparoscopic nephron-sparing surgery. The aim of this prospec-tive study was to evaluate the advantages of the use of fibringlue and collagen fleece in order to prevent hemorrhages dur-

Department of Urology, University of Turin, San Luigi Hospital, Orbassano (TO), Italy.

PORPIGLIA ET AL.424

ing laparoscopic partial nephrectomy (LPN) and to describe anapplication technique.

PATIENTS AND METHODS

Patients and data collection

From January 2001 to December 2005, a total of 74 pa-tients underwent laparoscopic nephron-sparing surgery for tu-mors in our center. The last 44 patients were considered fora comparative prospective study, and two groups were definedon the basis of the method of hemostasis chosen during theprocedure. Group A (n � 24) received only parenchymal su-ture and underwent the procedure before the patients in groupB (n � 20), who also received pro-coagulant fibrin glue (Tis-sucol®: fibrinogen, XIII coagulation factor, thrombin 500UI/mL; Baxter) and apposition of a platelet-aggregation pro-moter, horse-collagen fleece (Tissufleece®; Kollagen-re-sorb®). The two groups were similar in preoperative charac-teristics (Table 1). We compared the lesion diameter, operativetimes (minutes), warm-ischemia time (minutes), rate of trans-fusion, hemoglobin level on postoperative day 3, number ofhemorrhagic events, number of hematomas, and length of hos-pital stay in the two groups using the chi-square test or thetwo-tailed Student t-test.

Technique

A transperitoneal or retroperitoneal approach is chosen de-pending on the location of the renal mass (transperitoneal foranterior and medial lesions; retroperitoneal for posterior and lat-eral face lesions). Gerota’s fascia is opened, the ureter identi-fied, and the renal artery isolated. The peritumoral fat is left in-tact, and an ultrasound scan is performed using a laparoscopicprobe. During warm ischemia consequent to the clamping ofthe artery with a vascular bulldog, the resection is performedwith an electrocautery device and scissors. The specimen is im-mediately placed in an Endocatch® bag, which is removed atthe end of the procedure. A biopsy and frozen-section exami-nation of the bed of resection is performed only when tumorinfiltration is suspected. If the biopsy results are positive, weevaluate the options according to the individual case: radicalnephrectomy or deeper resection. Closure of the parenchyma is

performed with suture of the medulla at the level of the inter-lobar arteries and is completed with mattress suture (Fig. 1).

In group B, after suturing the parenchyma at the medullawith 3-0 Vicryl®, fibrin glue and collagen fleece were used.The collagen fleece is put in saline for 5 minutes and then cutextracorporeally so that it will fit the resection area; subse-quently, it is introduced through the 12-mm port and placed onthe kidney. The fibrin glue is diluted to 5 IU of thrombin with3 mL of calcium chloride solution in order to obtain a homo-geneous solution to promote coagulation. It is then introducedinto the abdomen through a 5-mm port and injected with a lap-aroscopic double jet probe (Duploject) onto the resection bedabove the collagen fleece (Fig. 2).

After apposing the collagen fleece (Fig. 3A, B), a wet com-press is applied for 2 minutes in order to compress the fleeceon the fibrin glue. The procedure is completed in the usual waywith mattress 2-0 absorbable suture over two strips of collagenfleece applied laterally to the margins of the resection area (Fig.3C, D).

TABLE 1. CLINICAL CHARACTERISTICS OF PATIENTS AND LESIONS

Group A (suture alone) Group B (suture �(n � 24) sealant) (n � 20) P value

Mean age (years) 60 � 13.5 (34–71) 59.7 � 12.3 (13–76)00 0.89Mean hemoglobin 14.5 � 2.6 (13–15.2) 14.0 � 1.9 (13.1–14.9) 0.78

(mg/dL)Mean diameter of lesion 3.3 � 1.2 (1–7.5). 3.0 � 1.3 (2–4)000. 0.59

at CT scan (cm)Side of lesion: R/L 15/9 11/9 0.89Location of lesion 0.96

Superior pole 10 12Inferior pole 4 4Central 10 4

FIG. 1. Closure of renal parenchyma with suture of medullaat level of interlobar arteries and completion with mattress su-ture.

LPN AND HEMOSTASIS USING SEALANTS 425

RESULTS

No significant statistical difference was observed betweenthe two groups in most of the intraoperative and perioperativefindings (Table 2). The mean operative time and mean warm-ischemia time were slightly (although not significantly) longerin group B, which could be accounted for by the 2.5 to 5 min-utes required to apply the glue and collagen fleece. The meanblood loss was 178 mL in group A and 219 mL in group B,and the mean postoperative hemoglobin level was slightly lowerin the latter. No patients in group A received intraoperativetransfusions, whereas the rate of transfusion in group B was10% (2 patients). The mean hospital stay was slightly but notsignificantly longer in group B (Table 2).

Among postoperative complications, we analyzed only the he-morrhagic events, as only these complications can be preventedby the use of sealants. In group A, four episodes of bleeding (twoacute and two hematomas) were observed. In the two cases ofacute bleeding, the patients presented low blood pressure and ab-

FIG. 3. Final steps. (A, B) Collagen fleece is apposed and covered with wet compress. (C, D) Mattress suture is applied to twostrips of collagen fleece.

FIG. 2. Injection of sealant onto collagen fleece through 5-mm port with double jet probe.

A

C

B

D

PORPIGLIA ET AL.426

dominal tension. On this basis, re-intervention by open surgerywas necessary, as well as heterologous blood transfusion. Dur-ing these procedures, interlobar artery bleeding was identifiedand closed. The two hematomas were evaluated by ultrasonog-raphy and found to be retroperitoneal with a diameter of 6 cm inone case and 7 cm in the other. Neither required intervention orblood transfusion. The CT scans performed at 6 months showedcomplete resolution of the hematomas. In group B, two cases ofacute bleeding were registered. The first one occurred 4 days af-ter the procedure with hematuria and clot retention and was sec-ondary to an arteriovenous fistula, which was treated with se-lective embolization. The second event occurred on the 7th

postoperative day with anemia. The patient required 3 bloodtransfusions and re-intervention, which identified interlobar-artery bleeding. No statistical differences were recorded betweenthe two groups for any of the variables considered. Because ar-teriovenous fistulas cannot be prevented by sealant, we considerthat there was only one bleeding episode in group B. Neverthe-less, the difference in the number of bleeding events in the twogroups was not statistically significant.

DISCUSSION

Although remaining a controversial specialized technique,LPN is gaining advocates throughout the world in all urologic

departments where advanced laparoscopy is performed. It hasbecome a routine treatment for selected renal masses that can-not be simply resected without occlusion of the artery, both inthe presence of a normal contralateral kidney and in some casesof solitary kidney.4,5 The technique has already demonstratedan oncologic efficacy similar to that of open procedures withfollow-ups of longer than 3 years.8–11 Furthermore, the meanwarm-ischemia time, another critical point of the laparoscopicapproach, does not seem to cause permanent renal-function im-pairment if maintained under 30 minutes12 or even, in our ex-perience, under 60 minutes.13 Nevertheless, the complicationsrepresent the most critical point that could impede the accep-tance of LPN as the best option. In the literature, there is stilla great discrepancy among authors in the rate of complications,which has reached 30% in some centers.6,7,14,15

Of all the complications, acute and chronic hemorrhage isthe most frequent and significant event. In order to decreasethese rates, various options have been proposed (Table 3). Theeasiest solution, proposed by Gill, is simple parenchymal su-ture of the bed of resection. Nevertheless, the same author re-ports a hemorrhage rate of 9.5% in 200 patients, a percentagethat is still too high to permit wider use of LPN. This is why,in recent years, research has been active to find new technolo-gies that would enable all the problems of hemostasis to besolved. High-pressure water-jet dissectors (Helmix Hydro jet;Erbe) have been successful in animals. Other devices such as

TABLE 2. PERIOPERATIVE PARAMETERS AND HEMORRHAGIC COMPLICATIONS

Group A Group B(suture alone) (suture � sealant) P value

Mean operative time (min) 116 � 26.6 (90–220) 130 � 23.5 (90–210) 0.68Mean ischemia time (min) 28.8 � 5.7 (18–60) 35.6 � 6.2 (20–52) 0.66Mean size of lesion (cm) 3.3 � 1.2 (1–8) 3.0 � 1.3 (2–5) 0.89Mean blood loss (mL) 178 � 34.5 (500–400) 219 � 44.6 (80–750) 0.93Mean hemoglobin (mg/dL) 11.9 � 1.2 (11–13) 11.5 � 1.5 (8.2–13.1) 0.71Rate of intraoperative transfusion (%) 0 10% (2 patients) 0.92Mean hospital stay (days) 5.9 � 1.2 (5–8) 6.3 � 2.1 (5–9) 0.68Postoperative acute hemorrhagic event 2 2 (one from arterio- —

venous fistula)Postoperative hematoma 2 0 —

TABLE 3. TECHNIQUES OF HEMOSTASIS

Rate ofSeries No. of patients Technique complications Rate of hemorrhage

Harmon et al 15 Ultrasonic shears � 0 0(2000)18 argon-beam coagulator

� Surgicel®

Bhayani et al Argon-beam coagulator 10.6 1.8(2004)5 � sealants � suture

Finley et al 15 Ultrasonic shears � 6 6(2005)22 argon-beam coagulator

� Surgicel® � Tisseel®

Janetschek (cited 78 Argon-beam coagulator 29 2.5by McDonough � fibrin glueand Morey21)

Gill et al (2006)4 200 Suture � Surgical® 33 9.5

the holmium:YAG laser or microwave tissue coagulator (Mi-croyaz OT-110 M; Heiwa Electronics Industry) have been usedwith fairly good results, but only on a few patients with shortfollow-up.10,16,17 Harmon and associates18 proposed the use ofultrasonic shears for the resection of the tumor, associated withthe argon-beam coagulator, obtaining encouraging results withno hemorrhages. However, once again, these series were small(15 patients).

Of all the hemostatic tools, sealants have had the most suc-cess. Introduced 9 years ago in urology, these agents have hada great influence on the development of modern surgical tech-niques.19 Their range of use goes from cardiovascular and car-diothoracic surgery to general surgery for gastroduodenal, he-patic, and splenic disease to the simplest use in dentistry.20

Many products are available, but in the urologic world, twohave shown success. Fibrin glue, unlike synthetic adhesives, of-fers the advantage of being biocompatible and biodegradable,and it does not induce inflammation, extended fibrosis, or tis-sue necrosis.21 Its mechanism of action consists of mimickingthe final steps of the physiological coagulation cascade to forma fibrin clot, as it is composed of concentrated fibrinogen andthrombin. The other sealants frequently used are collagen-basedadhesives.20 Made from a combination of bovine or equine col-lagen and bovine thrombin, they work by providing a matrixfor the clot and then assist coagulation by delivering fibrino-gen to the area (FloSeal®). These two products have been usedby various authors. Finley and colleagues22 employed them withultrasonic shears and the argon-beam coagulator, obtaining ahemorrhage rate of 6%. Richter and coworkers23 used them withultrasonic shears without any bleeding complication. Abukoraet al24 and Johnston and associates25 associated the argon-beamcoagulator with fibrin glue in 78 and 75 patients, respectively,recording 2 (2.5%) and 7 (9.3%) episodes of major bleeding.

In our experience, in order to evaluate the efficacy of onesystem of sealants, this prospective nonrandomized study wasset up in which two techniques (only suture v suture plussealants) were evaluated. We used fibrin glue (Tissucol®) di-luted with calcium chloride to obtain a homogeneous solutionand introduced into the abdomen through a 5-mm port with alaparoscopic double jet probe for application to the resectionbed above the surface of the collagen fleece. The horse-tendoncollagen fleece is able to act alone but also in association withTissucol. Collagen fleece alone in fact induces the activationof coagulation factors, which, when associated with fibrin glue,cause the genesis of a three-dimensional fibrin web to whichthe collagen free radicals become tightly attached by chemicalreactions to seal the resection area, promoting the cascade ofcoagulation and platelet activation. The fibrin is used as a pro-moter of coagulation, whereas the collagen as a top to the re-section area. This association (glue with collagen) is similar toFloSeal. The difference lies in the fact that in this last product,the collagen is already in a solution with the fibrin glue, whereasin our technique, the collagen was added in the form of a fleece.

Different brands of collagen fleece are available on the mar-ket, with differences in plasticity, size, and thickness. They areall cheap. The choice of the fleece depends on the surgeon’spreference (Tissufleece® is softer, whereas Kollagen resorb® isthicker and more resistant during knotting).

Even though no statistical difference was seen between ourgroups, we did not observe any chronic hemorrhages in group

B (sealant and suture) and only one acute hemorrhagic event,whereas in group A (suture only), four hemorrhagic events oc-curred. It is important to point out that only a few patients wereincluded in this study, and that this could influence the statis-tical evaluation.

The two hemostasis systems, suture and sealants, should beused together in order to obtain good control of bleeding. Inour opinion, using Tissucol and collagen fleece promotes co-agulation while facilitating suturing. The advantage of using fi-brin glue and collagen fleece is that during the mattress suture,the collagen fleece is easily pierced by the needle, unlike theclassic Surgicel® bolster, where the needle encounters great re-sistance, while maintaining sufficient force to impede lacera-tion of the renal parenchyma. One drawback of this procedureis the slightly longer warm-ischemia time necessitated by ap-plication of the sealant, which, in our experience, ranged from2.5 to 5 minutes.

In our opinion and from an analysis of literature, the use ofsealants does not completely resolve the problem of postopera-tive hemorrhages, especially acute events. The only way to en-sure the best hemostasis is to perform the most accurate suturepossible, while the use of sealants alone should be reserved forthe beds of small exophytic lesions, where renal-artery clampingis not necessary. It is important that in the future, in order to de-termine a standard hemostasis technique, rather than relying onthe development of sealants, we should rely on innovations insuture techniques, which represent the key element of bleedingcontrol, especially after resection of deeper and larger lesions.

CONCLUSIONS

Our results with the use of fibrin glues and collagen fleecewith suture in order to prevent hemorrhagic events after LPNcan be considered encouraging. As with all glue systems, how-ever, fibrin glue and fleece must be considered only for use asan adjuvant to help prevent chronic bleeding from small ves-sels. The suture remains the key component of hemostasis con-trol, as the sealants did not influence our results in any signif-icant way.

REFERENCES

1. Uzzo RG, Novick AC. Nephron sparing surgery for renal tumors:Indications, techniques and outcomes. J Urol 2001;166:6.

2. Gill IS, Matin SF, Desai M, et al. Laparoscopic partial nephrec-tomy for renal tumor: Duplicating open surgical techniques. J Urol2002;167:469.

3. Frank I, Colombo JR Jr, Rubinstein M, Desai M, Kaouk J, Gill IS.Laparoscopic partial nephrectomy for centrally located tumors. JUrol 2006;175:849.

4. Gill IS, Colombo JR, Moindazeh A, Finelli A, Ukimura O, TuckerK, Kaouk J, Desai M. Laparoscopic partial nephrectomy in soli-tary kidney. J Urol 2006;175:454.

5. Bhayani SB, Allaf ME, Link RE, Rao P, Varkakis JM, Jarrett TW,Kavoussi LR. Laparoscopic partial nephrectomy in patients withneoplasia in a solitary kidney. Urology 2004;64:35.

6. Thompson RH, Leibovich BC, Lohse CM, Zincke H, Blute M.Complications of contemporary open nephron sparing surgery: Asingle institution experience. J Urol 2005;174:855.

LPN AND HEMOSTASIS USING SEALANTS 427

PORPIGLIA ET AL.428

7. Ramani AAP, Desai MM, Steinberg AP, et al. Complications oflaparoscopic partial nephrectomy in 200 cases. J Urol 2005;173:42.

8. Link RE, Bhayani SB, Allaf ME, et al. Exploring the learning curve,pathological outcomes and perioperative morbidity of laparoscopicpartial nephrectomy performed for renal mass. J Urol 2005;173:1690.

9. Allaf ME, Bhayani SB, Rogers C, Varkarakis I, Link RE, InagakiT, Jarrett TW, Kavoussi LR. Laparoscopic partial nephrectomy:Evaluation of long term oncological outcome. J Urol 2004;172:871.

10. Moindazeh A, Gill IS, Finelli A, Kaouk J, Desai M. Laparoscopicpartial nephrectomy: 3 year follow-up. J Urol 2006;175:459.

11. Porpiglia F, Fiori C, Terrone C, Bollito E, Fontana D, Scarpa RM.Assessment of surgical margins in renal cell carcinoma afternephron sparing: A comparative study: Laparoscopy versus opensurgery. J Urol 2005;173:1098.

12. Bhayani SB, Koon RH, Pinto AM, Allaf ME, Trock BJ, JarrettTW, Kavoussi LR. Laparoscopic partial nephrectomy: Effect ofwarm ischemia on serum creatinine. J Urol 2004;172:1264.

13. Porpiglia F, Musso F, Terrone C, Renard J, Grande S, Poggio M,Scarpa RM. Can warm ischemia of more than 30 minutes, duringlaparoscopic nephron sparing surgery, cause damage of renal pa-renchyma: Prospective study and preliminary results. Presented atthe EAU Congress, Paris, 2006.

14. Wille AH, Tullmann M, Roigas J, Loening SA, Deger S. Laparo-scopic partial nephrectomy in renal cell cancer: Results and repro-ducibility by different surgeons in a high volume laparoscopic cen-ter. Eur Urol 2006;49:337.

15. Kim FJ, Rha KH, Hernandez F, Jarrett TW, Pinto PA, KavoussiLR. Laparoscopic radical versus partial nephrectomy: Assessmentof complications. J Urol 2003;170:408.

16. Lotan Y, Gettman MT, Ogan K, Baker LA, Caddedu JA. Clinicaluse of the holmium YAG laser in laparoscopic partial nephrectomy.J Endourol 2002;16:289.

17. Yoshimura K, Okubo K, Ichioka K, Terada N, Matsuta Y, Arai Y.Laparoscopic partial nephrectomy with a microwave tissue coag-ulator for small renal tumor. J Urol 2001;165:1893.

18. Harmon WJ, Kavoussi LR, Bishoff JT. Laparoscopic nephron spar-ing surgery for solid renal masses using the ultrasonic shears. Urol-ogy 2000;56:754.

19. Jackson MR. New and potential uses of fibrin sealants as an ad-junct to surgical hemostasis. Am J Surg 2001;182:36S.

20. Mankad PS, Codispoti M. The role of fibrin sealants in hemosta-sis. Am J Surg 2001;182:21S.

21. McDonough RC, Morey FA. Urological applications of tissueglues. American Urological Association Update Series.

22. Finley DS, Lee DI, Eichel L, Uribe CA, McDougall EM, Clay-man RV. Fibrin glue-oxidized cellulose sandwich for laparo-scopic wedge resection of small renal lesions. J Urol 2005;173:1477.

23. Richter F, Schnorr D, Deger S, Turk I, Roigas WA, Loening SA.Improvement of hemostasis in open and laparoscopically per-formed partial nephrectomy using a gelatin matrix thrombin tissuesealant (FloSeal). Urology 2003;61:73.

24. Abukora F, Nambirojan T, Albqani N, et al. Laparoscopic nephronsparing surgery: Evolution in a decade. Eur Urol 2005;47:488.

25. Johnston WK, Montgomery JS, Seifman BD, Hollenbeck BK,Wolf JS. Fibrin glue versus sutured bolster: Lessons learned dur-ing 100 laparoscopic partial nephrectomies. J Urol 2005;174:47.

Address reprint requests to:Francesco Porpiglia, M.D.

Dept. of UrologySan Luigi Hospital

Regione Gonzole 1010043, Orbassano

Torino, Italy

E-mail: porpiglia@libero.it

ABBREVIATIONS USED

CT � computed tomography; LPN � laparoscopic partialnephrectomy.