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TREATMENT REVIEW
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
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131
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
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Activates the conversion
of fibrinogen to fibrin
TachoSil (Nycomed)
Human
fibrinogen
and thrombin
fleece
Glutaraldehyde
crosslinks bovine
albumin to cell
proteins at wound
site to form a strong
adhesive
BioGlue (Cryolife)
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
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
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
References
133
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
46, 47
Hemostatic fibrin
sealant powder
Human
Ease of use
Uniform application
Lack of preparation time
Not yet commercially
available
Good results
48
Polyethylene
glycol hydrogel
Synthetic
Cyanoacrylates
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
Synthetic
51
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
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 patients 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
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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
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135
136
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
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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
15.
References
1.
2.
3.
4.
5.
6.
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8.
9.
10.
11.
12.
13.
14.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
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 patients 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.
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43.
44.
45.
46.
138
47.
48.
49.
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50.
51.
52.