Stesura Seveso


Archivio Italiano di Urologia e Andrologia 2016; 88, 3228

ORIGINAL PAPER

Bleeding during laparoscopic partial nephrectomy: 
Can a hemostatic matrix help to improve hemostasis?

Faruk Ozgor, Abdulmuttalip Simsek, Ozgu Aydogdu, Onur Kucuktopcu, Omer Sarilar, Ahmet Yalcin
Berberoglu, Mehmet Fatih Akbulut, Murat Binbay

Department of Urology, Haseki Teaching and Research Hospital, Istanbul, Turkey.

Objectives: To evaluate the possible role of
an hemostatic matrix on hemostasis, peri-

operative outcomes and complications in patients who under-
went laparoscopic partial nephrectomy (LPN). 
Materials and methods: Patients charts were analyzed retro-
spectively and their demographic characteristics, operative
parameters and follow-up results were recorded. Patients
were divided into two groups, according to those who used an
hemostatic matrix as Group 1 (n = 41) and those who did not
used as Group 2 (n = 44). Demographic characteristics of
patients, tumor features, operation time, clamping of the
renal vessels, ischemia time, suturing of the collecting sys-
tem, perioperative hemorrhage and complications were eval-
uated. Histopathological results, surgical margin status, crea-
tinine level and recurrence at the 3rd month of follow up were
analyzed. Statistical analyses were performed with SPSS
17.0 and significance was set at p value of < 0.05.
Results: The mean RENAL nephrometry score was 5.9 ± 2.0
and the mean tumor size was 35 ± 12 mm. All patients had a
single tumor and 44 of them had a tumor in the right kidney.
The renal artery was clamped in 79 cases and the mean
ischemia time was 20.1 ± 7 minutes. The mean tumor size
and the mean RENAL nephrometry score was statistically
higher in Group 1 (p: 0.016 and p < 0.001, respectively).
Pelvicaliceal repair was more common in Group 1 due to
deeper extension of tumors in this group (p: 0.038). In Group
1, less hemorrhage and blood transfusion requirement, with
shorter ischemia and operation time was detected. 
Conclusion: The outcomes of the recent study showed that
adjunctive use of an hemostatic matrix improves hemostasis
and decreases hemorrhagic complications during LPN.
Further prospective studies are required to assess the poten-
tial role of an hemostatic matrix in LPN.

KEY WORDS: Hemostatic matrix; Partial nephrectomy; 
Renal cell cancer.

Submitted 6 December 2015; Accepted 31 March 2016 

Summary

No conflict of interest declared.

tial complications including urinary leakage and bleed-
ing requiring transfusion (4). Since LPN was firstly
reported, several techniques for tumor excision and
hemostasis have been investigated to achieve a bloodless
operative field for precise tumor excision is an accept-
able ischemia time and with the least possible deteriora-
tion of renal function (5). However, use of the suture
techniques is time consuming and may cause addition-
al tissue damage (6). Some renal hemostatic agents have
been previously described for use during LPN, to
improve hemostasis and decrease complication rates.
However, there is no consensus on the routine use of
hemostatic agents during LPN. In a recent study, we
aimed to investigate the possible role of an hemostatic
matrix FloSeal (©FloSeal Baxter Healthcare Corporation)
on hemostasis, perioperative outcomes and complica-
tions in patients who underwent laparoscopic partial
nephrectomy (LPN).

MATERIAL AND METHODS
In our clinic, laparoscopic partial nephrectomy (LPN) for
renal tumours was performed in 85 patients by a single
surgeon between May 2009 and February 2014. In
patients with organ confined renal tumours with up to 7
cm in size, without lymph node and venous involvement,
LPN was performed. Informed consent was obtained from
all the patients. 
Patients’ charts were analyzed retrospectively and their
demographic characteristics, operative parameters and fol-
low-up results were recorded. 
Patients were divided into two groups, according to those
who used FloSeal as Group 1 (n = 41) and those who did
not used as Group 2 (n = 44).
A transperitoneal technique in the extended flank position
with three trocars was preferred in all the patients. If nec-
essary, additional trocar was inserted for liver or spleen
retraction and re-postioning of the kidney. After incision of
the Todt line, dissection continued medially to expose the
renal artery and vein. Endoscopic bulldog clamps were
used to interrupt blood flow, and peripheral small lesions
were resected without hilar clamping. Partial nephrectomy
was performed with monopolar scissors. Major transected
intrarenal were stiched up with eight sutures, while renal
parenchymal hemorrhage was kept.
Prepackaged hemostatic agent with a combination of 1.5

DOI: 10.4081/aiua.2016.3.228

INTRODUCTION
Previous studies demonstrated that nephron-sparing
surgery has similar oncologic outcomes in selected
patients when compared to radical nephrectomy (1, 2).
Laparoscopic partial nephrectomy (LPN) is a minimally
invasive nephron sparing technique with favorable renal
function outcomes, shorter hospital stay and decreased
postoperative analgesic use (3). However, LPN is a tech-
nical challenging procedure and associated with poten-



229Archivio Italiano di Urologia e Andrologia 2016; 88, 3

Bleeding during laparoscopic partial nephrectomy: Can a hemostatic matrix help to improve hemostasis?

ml of bovine gelatin matrix and 5000 US of bovine-
derived thrombin. 
This syringe was applied with an application device intro-
duced into the abdomen through a laparoscopic port. 
The renal artery was then unclamped to terminate warm
ischemia.
Demographic characteristics of the patients and tumor
features were compared between the two groups.
Intraoperative parameters including operation time,
clamping of the renal vessels, ischemia time, suturing of
the collecting system, perioperative hemorrhage and
complications were also evaluated. 
Hemorragic complication was defined as bleeding lead-
ing to convert open surgery or radical nephrectomy and
intraoperative or postoperative bleeding requiring trans-
fusion. Histopathological results, surgical margin status,
creatinine level and recurrence at the 3rd month of fol-
low up were also analyzed. 

Statistical analysis
Statistical analyses were performed with SPSS 17.0 (New
York, USA). 
Results were described as numbers, means, standard
deviations and percentages. Comparisons were per-
formed by the chi square test, Student t test and Mann
Whitney U test. 
Significance was set at p value of < 0.05.

RESULTS
The mean age and the mean BMI of all patients were
58.8+/-10.9 years old and 24.7+/-3.0 kg/m2.
All patients had a single tumour and 44 of them had a
tumour in the right kidney. Eight patients had an ASA
score of three, while hypertension and diabetes mellitus
were the most common comorbidities.
The mean RENAL nephrometry score was 5.9 ± 2.0 and
the mean tumor size was 35 ± 12 mm.
Demographic data are listed in Table 1. 
FloSeal was used in 41 patients and wedge resection was

N° Percentage (%)
Gender
Male 50 58.8%
Female 35 41.2%
Mean follow up time (months) 52.2+/-27.7
Mean BMI (kg/m2) 24.7+/-3.0
ASA score
1 52 61.2%
2 25 29.4%
3 8 9.4%
Comorbidities
None 50
Hypertension 24
Diabetes mellitus 19
Coronary arterial disease 6
Chronic obstructive pulmonary disease 5
Smoking
Yes 53 62.4%
No 32 37.6%
Radiological tumor location
Lower pole 42 49.4%
Middle pole 31 36.5%
Upper pole 12 14.1%
Complaint
Follow up 34 40%
Lower urinary tract symptoms 1 1.2%
Weakness 1 1.2%
Hematuria 9 10.6%
Weight loss 2 2.4%
Abdominal pain 2 2.4%
Flank pain 36 42.4%
Mean R.E.N.A.L. score 5.9+/-2.0
Mean tumor size (millimeters) 35+/-12

N° Percentage (%)
Mean preoperative hemoglobin (g/dl) 13.0+/-1.3
Mean preoperative creatinine (mg/dl) 1.09+/-0.35
Mean postoperative day one hemoglobin (g/dl) 12.0+/-1.5
Mean postoperative creatinine at 3rd month (mg/dl) 1.07+/-0.3
Side
Left 41 48.2%
Right 44 51.8%
Tumor extraction technique
Wedge resection 79 92.9%
Enucleation 6 7.1%
Hemostatic agent usage
Yes 41 48.2%
No 44 51.8%
Suturing of the collecting system
Yes 28 32.9%
No 57 67.1%
Turning to open surgery
Yes 4 4.7%
No 81 95.3%
Blood transfusion need
Yes 11 12.9%
No 74 87.1%
Mean perioperative hemorrhage (ml) 153.6+/-50.2
Mean operation time (minutes) 136.7+/-55.3
Perioperative complications
Hemorrhage 5 5.9%
Clavien complications
0 70 82.4%
1 10 11.8%
2 2 2.4%
3 3 3.6%
Mean ischemia time (minutes) 20.1+/-7
Mean hospitalization time (days) 3.5+/-1.6
Histology
Angiomyolipoma 13 15.3%
Complicated cyst 1 1.2%
Oncocytoma 3 3.5%
Renal cell cancer 68 80%
Grade of RCC
1 42
2 21
3 6
Pathological stage
T1a 65 76%
T1b 18 21.2%
T2 2 2.4%
Surgical margin
Negative 83
Positive 2
Recurrance at 3rd month follow up
Yes 0
No 85

Table 1. 
Preoperative demographic data of patients.

Table 2. 
Perioperative and post operative data of patients.



Archivio Italiano di Urologia e Andrologia 2016; 88, 3

F. Ozgor, A. Simsek, O. Aydogdu, O. Kucuktopcu, O. Sarilar, A. Yalcin Berberoglu, M. Fatih Akbulut, M. Binbay

230

the most common technique for partial nephrectomy.
The renal artery was clamped in 79 cases and the mean
ischemia time was 20.1 ± 7 minutes. 
The mean perioperative hemorrhage was 153.6+/-50.2
ml and blood transfusion was required in 11 patients.
Suturing of the collecting system was performed in 28
patients. The most common histopathology was renal
cell carcinoma and angiomyolipoma. Patients’ preopera-
tive data and pathological results are detailed in Table 2.
The mean tumor size and the mean RENAL nephrome-
try score was statistically higher in Group 1 (p = 0.016
and p < 0.001, respectively). 
Pelvicaliceal repair was more common in Group 1 due to
deeper extension of tumors in this group (p: 0.038).  
In Group 1, use of FloSeal provided better bleeding con-
trol with less hemorrhage and blood transfusion require-
ment. Because of the less stiches requirement in group 1,
the mean ischemia time and the time operation were
18.2 and 115.6 minutes, respectively and these parame-
ters were shorter in group 1 when compared with Group
2 (p = 0.038). None of the laparoscopic procedures in
Group 1 was converted to open surgery whereas in
Group 2, four patients were converted to open surgery
due to uncontrolled bleeding in two, decision for radical
nephrectomy in one and technique difficulty in one.
Comparison between the two groups is summarized in
Table 3.

DISCUSSION
Although previous studies have shown that LPN is a fea-
sible and effective minimally invasive technique in the
surgical treatment of selected patients with renal tumors,
its potential risk of bleeding requiring transfusion is well
known (7, 8). Bleeding should be minimized to avoid
hypovolemia, anemia, hemodynamic deterioration and
exposure to the risk of transfusion (9). It is also impor-
tant to achieve optimal visualization of the surgical site
to enabling an acceptable ischemia time and oncologic
outcome (10). Control of bleeding in LPN, is an active
area of investigation since uncontrolled hemorrhage neg-
atively affects the mortality and morbidity rates, as well
as the convalescence period.
Traditional surgical methods including suture, energy
based coagulation systems, ligature and hemostatic clips
can be used to handle bleeding (12, 13). 
Available hemostatic agents include absorbable hemo-
stats such as gelatin, collagen and oxidized regenerated
cellulose and active hemostats such as thrombin and fib-
rin sealants (16).
Fibrin sealants were reported as easy to use but not effec-
tive in dealing with major vascular injury. 
Therefore, a combination of different hemostasis meth-
ods has been investigated (17).
In a previous study the authors compared seven hemo-
static agents in an animal partial nephrectomy model
(17). The authors concluded that hemostatic agents were

Hemostatic agent usage
Yes No P value

Number 41 44
Mean age (years) 56.8 60.7 0.101
Mean follow up time (months) 39+/-17.2 64.4+/-24.5 < 0.001
Mean BMI (kg/m2) 25.2 24.3 0.169
ASA score 0.365
Tumor size (mm) 38.2 32 0.016
Mean R.E.N.A.L. score 6.8 5.1 < 0.001
Mean hemoglobin drop (g/dl) 1.01 1.07 0.842
Mean creatinine level change (mg/dl) 0.04 - 0.02 0.143
Mean perioperative hemorrhage (ml) 132.9 172.9 < 0.001
Mean operation time (minutes) 115.6 156.4 < 0.001
Mean ischemia time (minutes) 18.2 21.9 0.013
Mean hospitalization time (days) 3.4 3.6 0.555
Comorbities
None 27 23 0.399
Hypertension 9 13
Diabetes mellitus 8 10
Coronary arterial disease 0 5
Chronic obstructive pulmonary disease 2 3
Complaint 0.151
Follow up 19 15
Lower urinary tract symptoms 0 1
Weakness 1 0
Hematuria 1 8
Abdominal pain 1 1
Flank pain 17 19
Smoking
Yes 23 30 0.251
No 18 14
Radiological tumor location
Lower pole 18 24
Middle pole 17 14
Upper pole 6 6
Tumor extraction technique 0.108
Wedge resection 40 39
Enucleation 1 5
Turning to open surgery 0.048
Yes 0 4
No 41 40
Blood transfusion need 0.005
Yes 1 10
No 40 34
Clamping of the renal vessels 0.112
Yes 36 43
No 5 1
Perioperative complication 0.084
Hemorrhage 0 5
Clavien complications 0.422
0 35 35
1 4 6
2 1 1
3 1 2
Histology 0.264
Angiomyolipoma 7 6
Complicated cyst 0 1
Oncocytoma 0 3
Renal cell cancer 34 34
Grade of RCC 0.044
1 16 26
2 15 6
3 3 3
Pathological stage 0.298
T1a 29 36
T1b 10 8
T2 2 0
Surgical margin 0.960
Negative 40 43
Positive 1 1

Table 3. 
Comparison of patients according to

perioperative hemostatic agent usage.



231Archivio Italiano di Urologia e Andrologia 2016; 88, 3

Bleeding during laparoscopic partial nephrectomy: Can a hemostatic matrix help to improve hemostasis?

effective for small vascular injuries. However, sutured
bolsters were required for large partial nephrectomies.
Hutchinson et al. (11) evaluated the effectiveness of fibrin
pad consisting of human thrombin and fibrinogen deliv-
ered to the targeted site by an absorbable synthetic
matrix in an animal model. The authors have demon-
strated that fibrin pad was as effective as conventional
methods for the primary management of severe bleeding
without the need for hilar control with a shorter opera-
tive time. 
Dalpiaz et al. (19) reviewed the use of hemostatic agents
in 15 animal model studies and 11 clinical trials con-
cluding that fibrin sealants were effective in both animal
and clinical studies. Richter et al. and Bak et al. (20, 21)
investigated the use of FloSeal in LPN in two different
studies. In both studies no renal suturing was used, none
of the patients underwent pelvicaliceal repair and none
of the patients required blood transfusions. Gill et al. (6)
evaluated the use of FloSeal during LPN. 
The authors found that the adjunctive use of FloSeal
 substantially enhanced parenchymal hemostasis and
decreased the procedural and hemorrhagic complica-
tions.
LPN with the use of FloSeal is a feasible and safe method
for the treatment of small renal tumour.
FloSeal facilitates the conversion of fibrinogen to fibrin
and creates an insoluble fibrin clot acting as a hemostat-
ic sealant. FloSeal includes gelatin granules, which swell
in case of hemorrhage and mechanically control the
bleeding by creating a composite hemostatic plug.
FloSeal can be injected through a single laparoscopic port
with a short application time and does not require a
completely dry surgical field to be effective. 
Disadvantages of FloSeal include cost, possible allergic
reactions and potential transmission of prion diseases
(22). In the present study, FloSeal was used as single
hemostatic agent in all the patients. None of the patients
experienced adverse effect associated with FloSeal.
Suturing was used for renal collecting system repair, in
case of major transected intrarenal vessels and severe
parenchymal hemorrhage. 
Intraoperatively, hemostasis was sufficient in all the
patients. Mean tumor size and mean warm ischemia time
were 35+/-12 mm and 20.1+/-7 minutes, respectively.
These were comparable with previous studies (4, 5, 17).
Previous studies described an association between the
depth of tumor invasion and rate of hemorrhage.
Ramani et al. (22) investigated complications associated
with LPN and showed that 53% of 19 patients requiring
transfusion due to hemorrhage had deep tumors. 
In this study, the FloSeal group tended toward signifi-
cantly fewer hemorrhagic complications although the
depth of tumor invasion was higher. Our findings
showed that FloSeal provides better bleeding control
with less hemorrhage and blood transfusion require-
ments, with significantly shorter operation and warm
ischemia time. Although our findings support previous
trials advocating that FloSeal is a safe and effective hemo-
static agent, we think that it should be used as an adjunc-
tive method in conjunction with suturing techniques, for
major bleedings from large vessels or renal parenchyma.
Although the current study is one of the rare studies

investigating the use of FloSeal as a hemostatic agent in
LPN, it has some limitations including its retrospective
design and relatively small number of patients.
In conclusion, FloSeal is a safe,reliable and effective
hemostatic agent, which can be used during LPN to
avoid hemorrhagic complications. FloSeal may poten-
tially enhance the technique of LPN and help the sur-
geon to perform the procedure more comfortably. 
Further prospective, randomized and controlled stud-
ies are required to evaluate the potential role of FloSeal
in LPN.

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Correspondence
Faruk Ozgor, MD
md.farukozgor@yahoo.com

Abdulmuttalip Simsek, MD
simsek76@yahoo.com

Ozgu Aydogdu, MD
Onur Kucuktopcu, MD
Omer Sarilar, MD
Ahmet Yalcin Berberoglu, MD
Mehmet Fatih Ahbulut, MD
Murat Binbay, MD
Department of Urology, Haseki Teaching and Research Hospital
Millet Cad. No: 11, 34096, Fatih, Istanbul, Turkey