Safety of En Bloc Ligation of the Renal Hilum During Laparoscopic Radical Nephrectomy for Renal Cell Carcinoma: A Randomized Controlled Trial

Abstract

Aim:

To evaluate the safety of en bloc stapler ligation of the renal vascular pedicle during laparoscopic radical nephrectomy for renal cell carcinoma.

Subjects and Methods:

Clinical data were collected prospectively from 70 patients who underwent either en bloc stapling of the renal hilum (n=35) (Group A) or the separate ligation method (n=35) (Group B) to treat renal cell carcinoma. To evaluate the incidence of arteriovenous fistula (AVF), blood pressure and heart rate were measured, and abdominal auscultation was performed at 1 month, 3 months, 6 months, and 12 months post-surgery. Abdominal computed tomography was also performed at 6 and 12 months post-surgery. In addition, preoperative characteristics and postoperative outcomes (such as operation time and estimated blood loss [EBL]) were examined.

Results:

Both operation time and EBL were lower for Group A: operative time, Group A versus Group B, 60.26±10.94 minutes versus 67.51±10.49 minutes (P=.007); EBL, Group A versus Group B, 33.53±13.46 mL versus 49.14±32.21 mL (P=.011). No statistically significant differences were noted in either of the postoperative variables (blood pressure and heart rate), and there was no clinical evidence of bruit or AVF at 12 months post-surgery.

Conclusions:

No AVF was observed after en bloc ligation upon clinical follow-up or on radiological evaluation.

Introduction

Laparoscopic radical nephrectomy (LRN) is a surgical procedure commonly used for patients with renal cell carcinoma (RCC) that is not amenable to nephron-sparing surgery.^1,2 Separate stapling of the renal artery and vein during LRN involves the laparoscopic removal of the tissues attached to each vessel. This is time consuming and carries an increased risk of injuring the vessels, potentially causing a massive hemorrhage.³

An alternative method, known as the en bloc stapling technique, involves stapling the artery and vein together; however, this method is also associated with complications such as arteriovenous fistula (AVF).⁴ Recently, Schatloff et al.⁵ showed that en bloc stapling did not increase the incidence of AVF during laparoscopic nephrectomy. However, to date, no prospective randomized controlled trials examining the incidence of AVF after en bloc stapling during LRN for RCC have been performed. Therefore, the present study compared en bloc stapling of the renal hilum during LRN with a technique that involves dissecting out the artery and vein and ligating them separately. The postoperative stability of the en bloc ligation technique was then examined.

Patients and Methods

Patients and study design

In total, 70 patients who were clinically diagnosed with RCC between May 2008 and September 2010 and who satisfied the inclusion and exclusion criteria were recruited to the study. The study was approved by the local Institutional Review Board.

Patients who (1) were radiologically diagnosed with RCC≤T2N0M0, (2) were able to move around freely and perform activities of daily living, and (3) were willing and able to participate in the study were included. The following patients were excluded: (1) patients who could be treated with nephron-sparing surgery (assessed as “low risk” according to the 2007 European Association of Urology RCC guidelines⁶), (2) patients assessed as “intermediate risk,” who elected to undergo nephron-sparing surgery, (3) patients who had previously undergone laparotomy, (4) patients with a history of ipsilateral renal surgery, and (5) patients with suspected, or with a history of, perinephric inflammation.

The patients were informed about the advantages and disadvantages of each technique. Informed consent was obtained from each patient, along with an agreement to enter the randomization process. Thus patients who met the inclusion criteria were randomized by simple block randomization and underwent either en bloc ligation (n=35) (Group A) or separate ligation (n=35) (Group B).

Surgical technique

For both groups, laparoscopic nephrectomy was performed by a single surgeon using a transperitoneal approach. En bloc stapling was performed by identifying the renal hilum (with no dissection of the fibrolymphatic tissue). The renal artery and vein were then stapled simultaneously using an endovascular GIA™ stapler (Echelon Flex™ 60 mm, 2.5 load Endocutters; Ethicon Endo-Surgery, Cincinnati, OH). For the control group, the renal artery and vein were dissected, separated, and ligated individually; the renal artery was ligated using clips, and the renal vein was ligated using staples (Fig. 1).

FIG. 1.

En bloc ligation of the renal artery (a) and vein (v) during laparoscopic radical nephrectomy.

Assessment of efficacy and safety

The primary end point was the occurrence of AVF at 1 year post-surgery. The secondary end points were operative time, estimated blood loss (EBL), and complications.

Patients were screened before enrollment to determine whether they met the inclusion or exclusion criteria. Information regarding past medical history was also collected. A physical examination, routine hematologic examinations, and renal function tests were also performed. Blood pressure and heart rate were measured, and abdominal auscultation was performed at each visit (at the pre-enrollment screening and 1 month, 3 months, 6 months, and 12 months postoperatively) to diagnose AVF. In addition, abdominal computed tomography (CT) was performed at 6 and 12 months postoperatively. Operative time, EBL, pathologic findings, and complications were also documented to compare the surgical outcome between the two groups.

Statistical analysis

Statistical analysis was performed using intent-to-treat analysis. Operative time and EBL during the operation were assessed using Student's t test. In addition, the location of the renal mass, the clinical stage, postoperative pathologic findings, and complications were compared using the chi-squared test. SPSS version 18.0 software (SPSS, Inc., Chicago, IL) was used for all statistical analyses, and a P value of <.05 was considered statistically significant.

Results

One subject from Group A was lost to follow-up and therefore excluded. Data collected from the medical records of the 34 and 35 patients in the en bloc ligation and separate ligation groups, respectively, who completed the study were analyzed (Fig. 2).

FIG. 2.

Participation flowchart.

There were no statistically significant differences in preoperative characteristics between the two groups. The size of the renal mass in Group A was 6.24±1.87 cm, and that in Group B was 6.52±1.52 cm (P=.498). There was no significant difference in preoperative clinical stage between the two groups (P=.263) or in the side (left or right) presenting with RCC (P=.536) (Table 1). Two patients in Group B experienced renal vein injury during dissection to separate the artery and vein, and one required conversion to an open procedure. The operation time was 60.26±10.94 minutes for Group A and 67.51±10.49 minutes for Group B (P=.007). EBL was 33.53±13.46 mL for Group A and 49.14±32.21 mL for Group B (P=.011). Upon postoperative histopathologic examination, 32 patients in Group A were diagnosed with RCC, 1 with cystic nephroma, and 1 with oncocytoma. In Group B, 33 patients were diagnosed with RCC, 1 with angiomyolipoma, and 1 with oncocytoma. Three patients in Group A and 2 patients in Group B required a blood transfusion on post-surgical Day 1 (Table 2). No patient was diagnosed with AVF upon abdominal CT performed at 6 and 12 months postoperatively (Fig. 3). In addition, no bruit was heard on abdominal auscultation, and there were no significant differences in blood pressure or heart between the two groups. There was no evidence of AVF in either group at 1, 3, 6, or 12 months postoperatively (Table 3).

FIG. 3.

Reconstructed computerized tomographic arteriographs obtained post-surgery: (A) 6 months and (B) 12 months post-surgery.

Table 1.

Preoperative Characteristics

	Group A (n=34)	Group B (n=35)	P value
Age (years)	60.12±11.64	61.09±13.25	.748
BMI (kg/m²)	23.94±3.00	25.17±3.30	.108
Size of renal mass (cm)	6.24±1.87	6.52±1.52	.498
Clinical stage			.263^a
T1b	12	16
T2	22	19
Side of renal mass			.536^a
Right	22	22
Left	12	13

Group A received en bloc ligation; Group B underwent the separate method.

P values were calculated by Student's t-test unless designated otherwise.

By chi-squared test.

BMI, body mass index.

Table 2.

Comparison Between the Separate and En Bloc Groups

	Group A	Group B	P value
Operative time (minutes)	60.26±10.94	67.51±10.49	.007
Estimated blood loss (mL)	33.53±13.46	49.14±32.21	.011
Pathology specimen			.550^a
Renal cell carcinoma	32	33
Cystic nephroma	1	0
AML	0	1
Oncocytoma	1	1
Complication			.111^a
Postoperative transfusion	3	2
Renal vein injury	0	2
Open conversion	0	1
Suspicion of AVF	0	0

Group A received en bloc ligation; Group B underwent the separate method.

P values were calculated by Mann–Whitney test unless designated otherwise.

By chi-squared test.

AML, angiomyolipoma; AVF, arteriovenous fistula.

Table 3.

Comparison of Hemodynamic Parameters Between Group A and Group B

	Group A	Group B	P value
Preoperative
Heart rate (beats/minute)	78.59±2.49	79.03±3.29	.534
Blood pressure (mm Hg)
Systolic	120.29±10.87	121.14±12.31	.762
Diastolic	76.47±7.34	78.00±8.68	.432
1 month postoperatively
Heart rate (beats/minute)	77.88±1.97	78.46±4.20	.472
Blood pressure (mm Hg)
Systolic	119.12±8.66	119.43±9.38	.887
Diastolic	80.00±7.79	78.86±6.76	.518
3 months postoperatively
Heart rate (beats/minute)	77.12±1.86	77.71±3.92	.424
Blood pressure (mm Hg)
Systolic	119.71±7.97	119.14±8.87	.782
Diastolic	77.65±6.54	77.43±6.57	.890
6 months postoperatively
Heart rate (beats/minute)	77.65±2.23	77.49±3.03	.802
Blood pressure (mm Hg)
Systolic	117.94±7.70	120.57±10.56	.241
Diastolic	79.41±6.94	80.29±6.64	.595
12 months postoperatively
Heart rate (beats/minute)	78.24±2.50	77.31±3.18	.186
Blood pressure (mm Hg)
Systolic	119.71±8.70	116.57±8.73	.140
Diastolic	80.29±7.17	77.71±8.08	.165

Group A received en bloc ligation; Group B underwent the separate method.

P values were calculated by Student's t-test unless designated otherwise.

Discussion

En bloc ligation of the renal hilum during laparoscopic nephrectomy did not carry a higher risk of complications than separate ligation. In addition, the operating time was shorter than that for the separate ligation method.

Post-nephrectomy AVF is a rare complication. According to a literature review by Lacombe,⁷ approximately 60 cases were reported in 40 years (from 1934); however, en bloc stapling appeared to increase the risk of AVF. AVF results in increased venous congestion and can cause tachycardia or rapid cardiopulmonary decompensation. It may even cause severe cardiac failure and death.⁸ Thus en bloc stapling of the renal hilum during nephrectomy has been avoided.

However, Baptista-Silva et al.⁹ showed that inflammation and remnant tumor fragments increased the risk of post-nephrectomy AVF. The studies showing that en bloc stapling increases the incidence of AVF all included patients undergoing nephrectomy due to infection and trauma; this may have affected the outcomes, leading to the erroneous suggestion that en bloc stapling increases the risk of AVF.¹⁰ When en bloc stapling is performed, the presence of inflammation (caused by infection or trauma) or the suture material (which acts as a foreign body and can cause tissue erosion) can increase the risk of AVF.¹¹ The present study excluded patients with evidence of perinephric inflammation or untreated pyuria on preoperative CT scans and urine analysis to avoid inflammation-induced AVF.

Other reports have retrospectively evaluated patients who underwent en bloc stapling during nephrectomy and found no evidence of AVF (Table 4). These studies were performed exclusively in patients with RCC, but included those undergoing nephroureterectomy to treat urothelial cell carcinoma and those undergoing simple nephrectomy to remove a benign mass or a nonfunctional kidney. The present study is the first randomized controlled trial of the en bloc stapling method for LRN in patients with RCC. Similar to previous studies, the present study found no evidence of AVF on CT scans performed 6 months and 12 months postoperatively or on careful abdominal auscultation and observation of vital signs at each follow-up visit.

Table 4.

Published Studies of En Bloc Stapling of Renal Hilum During Nephrectomy

Reference	Study	Approach	En bloc (n)	Operation time (minutes)	EBL (mL)	Follow-up (months)	Open conversion	Other complications (n)
Rapp et al.¹³	Retrospective single arm	Laparoscopic	26	NR	NR	26 (6–49)	NR	Incisional cellulitis (1); Port-site hernia (1)
Kouba et al.¹¹	Prospective double arm	Laparoscopic	90	NR	173	34	3	NR
White et al.¹⁴	Retrospective single arm	Open and HALS	94	58 (42–94)	113.20±309.93	35.2 (6–79)	NR	NR
Buse et al.¹⁵	Retrospective single arm	Laparoscopic	57	145 (95–410)	100 (50–1000)	12	0	Acute bleeding (2); Hematoma evacuation (1)
Ou et al.¹⁶	Retrospective single arm	HALS	23	177.3 (135–343)	117 (50–500)	24.5	0	Pneumonia (1); Wound hematoma (1)
Conradie et al.¹⁰	Retrospective double arm	Laparoscopic	93	56 (22–130)	32 (0–200)	28 (1–44)	2	Iliac fossa pain (1); Wound sepsis (1); Port-site hernia (2); Diaphragm injury (1)
Schatloff et al.⁵	Retrospective double arm	Laparoscopic	65	130 (119–141)	100 (39–160)	25	NR	Skin hematoma (1); Lung atelectasia (1); Bowel injury (1); Bowel eventration (1); Pulmonary edema (1); Acute coronary disease (1)
Present study	Prospective double arm	Laparoscopic	34	57.95 (47–85)	36 (20–50)	12	0	Delayed bleeding (3)

AVF, arteriovenous fistula; EBL, estimated blood loss; HALS, hand-assisted laparoscopic surgery; NR, not reported.

The removal of the renal hilum during laparoscopic nephrectomy is very difficult because it contains major blood vessels such as the renal artery and vein and the vena cava, which are surrounded by fibrolymphatic tissue. In addition, laparoscopic surgery carries the risk of massive bleeding due to damage caused to the major vessels, which may then require conversion to an open procedure. On the other hand, en bloc stapling does not involve as much hilar dissection as other methods that involve ligating the renal artery and vein separately. In the present study, renal vein injury occurred in 2 patients in the control group, one of whom required conversion to an open procedure. Also, blunt dissection was used to separate the perihilar tissues, and, unlike the separate ligation method, no dissection was performed inside the renal hilum. Significant differences in EBL (due to bleeding resulting from the dissection process or by injury to the major vessels) were observed between the two groups. Stapling is one of the safest ways to ligate blood vessels, and the failure rate is less than 0.5% (if cases of inappropriate use are excluded).¹² To ensure appropriate stapling, the instrument must be in good condition before the procedure. The surgeon should also confirm the absence of solid material (such as clips) from the tissues. In addition, there must be plenty of space between the great vessels and the kidney. All of the tissues to be stapled must be positioned correctly between both jaws. If device failure occurs, then clips and an endosuction device are placed into the peritoneal cavity; the jammed staple should then be released using the emergent release button. Additional clips should be used at incompletely ligated sites. However, clipping of the renal artery requires sufficient dissection and much caution because there is a risk of vessel injury should the clip slip.³

Using a stapler during radical nephrectomy is more expansive than using Hem-o-lok^® (Weck Surgical Instruments, Teleflex Medical, Durham, NC) clips or other clips. However, we found that en bloc stapling resulted in shorter operation times and a lower risk of bleeding, which may reduce the overall cost of the procedure. Thus, en bloc stapling may be an appropriate alternative to separation ligation.

The present study has several limitations. The follow-up period was relatively short, and the sample number was small. In addition, ligation of the renal artery and vein using a stapler would be a more suitable design for the control group. Despite these limitations, this is the first randomized controlled study conducted to evaluate the safety of en bloc stapling of the renal hilum during LRN and to examine its effects on the incidence of AVF. Further long-term follow-up studies involving a larger sample number are required to confirm these results.

Conclusions

En bloc stapler ligation of the renal vascular pedicle during LRN for RCC appears to be safe, and the results are comparable with those obtained when the vessels are ligated separately.

Footnotes

Acknowledgment

This study was supported by Dong-A University Academic Fund.

Disclosure Statement

No competing financial interests exist.

References

Berger

, Brandina

, Atalla

, Herati

, Kamoi

, Aron

, Haber

, Stein

, Desai

, Kavoussi

, Gill

. Laparoscopic radical nephrectomy for renal cell carcinoma: Oncological outcomes at 10 years or more. J Urol, 2009; 182:2172–2176.

Saranchuk

, Savage

. Laparoscopic radical nephrectomy: Current status. BJU Int, 2005; 95,Suppl 2:21–26.

Schatloff

, Lindner

. Current status of en bloc stapling of the renal hilum during laparoscopic nephrectomy. J Laparoendosc Adv Surg Tech A, 2010; 20:631–633.

Kajbafzadeh

, Broumand

. Arteriovenous fistula following nephrectomy. Eur Urol, 1997; 31:112–114.

Schatloff

, Ramon

, Lindner

, Kitrey

, Dotan

, Nahtomi-Shick

, Nadu

. Is postoperative arteriovenous fistula still a concern after en bloc stapling of the renal hilum during laparoscopic nephrectomy? J Endourol, 2009; 23:639–643.

Ljungberg

, Hanbury

, Kuczyk

, Merseburger

, Mulders

, Patard

, Sinescu

. Renal cell carcinoma guideline. Eur Urol, 2007; 51:1502–1510.

Lacombe

. Renal arteriovenous fistula following nephrectomy. Urology, 1985; 25:13–16.

Ozaki

, Kubo

, Hanayama

, Hatada

, Shinagawa

, Maeba

, Hirata

, Aoki

, Kodama

, Aizawa

. High-output heart failure caused by arteriovenous fistula long after nephrectomy. Heart Vessels, 2005; 20:236–238.

Baptista-Silva

, de Figueiredo

, Castro

, Verissimo

, Camara

. Postnephrectomy arteriovenous fistula. Sao Paulo Med J, 1997; 115:1444–1447.

10.

Conradie

, Urry

, Naidoo

, Mahmood

, Jogiat

, Alsharef

, Mierzwinski

. Advantages of en bloc hilar ligation during laparoscopic extirpative renal surgery. J Endourol, 2009; 23:1503–1507.

11.

Kouba

, Smith

, Derksen

, Gunn

, Wallen

, Pruthi

. Efficacy and safety of en bloc ligation of renal hilum during laparoscopic nephrectomy. Urology, 2007; 69:226–229.

12.

Deng

, Meng

, Nguyen

, Bellman

, Stoller

. Laparoscopic linear cutting stapler failure. Urology, 2002; 60:415–419discussion 419–420.

13.

Rapp

, Orvieto

, Gerber

, Johnston

3rd , Wolf

Jr , Shalhav

. En bloc stapling of renal hilum during laparoscopic nephrectomy and nephroureterectomy. Urology, 2004; 64:655–659.

14.

White

, Klein

, Gash

, Waters

. Prospective radiographic followup after en bloc ligation of the renal hilum. J Urol, 2007; 178:1888–1891discussion 1891.

15.

Buse

, Gilfrich

, Pfitzenmaier

, Bedke

, Haferkamp

, Hohenfellner

. En bloc stapler ligation of the renal vascular pedicle during laparoscopic nephrectomy. BJU Int, 2008; 101:878–882.

16.

, Yang

, Tzai

. En bloc stapling of renal hilum during hand-assisted retroperitoneoscopic nephroureterectomy in dialysis patients. Urology, 2008; 72:589–592.