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FIBRIN GLUE-OXIDIZED CELLULOSE SANDWICH FOR LAPAROSCOPIC WEDGE RESECTION OF SMALL RENAL LESIONS
0022-5347/05/1735-1477/0 THE JOURNAL OF UROLOGY® Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 173, 1477–1481, May 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000154165.12738.7f
Oncology: Renal/Upper Tract/Bladder FIBRIN GLUE-OXIDIZED CELLULOSE SANDWICH FOR LAPAROSCOPIC WEDGE RESECTION OF SMALL RENAL LESIONS DAVID S. FINLEY, DAVID I. LEE, LOUIS EICHEL, CARLOS A. URIBE, ELSPETH M. MCDOUGALL* , AND RALPH V. CLAYMAN† ‡ From the Department of Urology, University of California-Irvine, Orange, California
ABSTRACT
Purpose: We present our experience with standard laparoscopic wedge resection of small renal tumors using a fibrin glue-oxidized cellulose sandwich for hemostasis. Materials and Methods: From May 2002 to December 2003, 15 patients underwent laparoscopic wedge resection for a total of 15 nonhilar renal masses. Renal hilar clamping was performed in 1 patient and no sutures were placed. We used ultrasonic shears and an argon beam coagulator to resect and then coagulate the tumor bed. Tisseel (Baxter Corp., Deerfield, Illinois) was applied to the resection bed, followed by a layer of oxidized, regenerated cellulose (Surgicel, Ethicon, Somerville, New Jersey) and a final layer of Tisseel. Results: Mean preoperative tumor size was 2.2 ⫻ 2.2 ⫻ 2.1 cm. Lesions were subdivided based on the percent of the lesion that extended beyond the renal parenchymal border on computerized tomography as exophytic— greater than 60% in 6 cases, endophytic—less than 40% in 4 and mesophytic— 40% to 60% in 5. Mean operative time was 3.8 hours (range 3 to 5). Mean blood loss was 108 ml (range 20 to 300). No patient required blood transfusion. There was no significant difference in blood loss or change in creatinine among the endophytic, exophytic and mesophytic groups (150, 121 and 93 ml, and 0.03, 0.07 and 0.04 mg/dl, respectively). Margin status was negative in all cases (mean thickness 3.2 mm). Average hospital stay and time to the resumption of oral intake were 2.7 and 1.4 days, respectively. Conclusions: Small exophytic or mesophytic renal lesions can be safely excised laparoscopically without vessel clamping. Excellent hemostasis was achieved in each case with the newer hemostatic agents. KEY WORDS: kidney; carcinoma, renal cell; laparoscopy; nephrectomy; nephrons
Current minimally invasive nephron sparing techniques for small renal masses include laparoscopic partial nephrectomy (LPN) and laparoscopic wedge resection (LWR). Renal parenchymal hemostasis before and during dissection has been achieved using the classic open techniques of renal vascular clamping, hand assisted vascular/parenchymal control and intracorporeal suturing. However, the advent of newer forms of hemostatic instrumentation and agents may simplify the approach. At our hospital we have successfully used the ultrasonic shears and argon beam coagulator (ABC), followed by topical application of a Tisseel-Surgicel sandwich to achieve sutureless hemostasis during LWR for small renal masses. MATERIALS AND METHODS
From May 2002 to December 2003, 12 male and 3 female patients with an average age of 68 years (range 53 to 83), a Submitted for publication July 13, 2004. * Financial interest and/or other relationship with Applied Medical Resources, Yamanouchi Pharma America, Intuitive Surgical, Storz Endoscopy America, Ethicon Endo-Surgery and Simbionix. † Financial interest and/or other relationship with Applied Medical, Endocare, Greenwald, Microvasive, Cook Urological, Orthopedic Systems, Yamanouchi Pharma, Simbionix, Intuitive Surgical, Ethicon Endo-Surgery and Storz Endoscopy. ‡ Correspondence: Department of Urology, University of California, Irvine Medical Center, 101 The City Dr., Building 55, Room 304, Orange, California 92868 (telephone: 714-456-3330; FAX: 714-4565062; e-mail: [email protected]).
mean American Society of Anesthesiologists score of 2.4 (range 2 to 4) and nonhilar cT1N0M0 enhancing renal lesions underwent LWR for a total of 15 renal masses (table 1, part A of figure). Mean computerized tomography (CT) tumor size was 2.2 ⫻ 2.2 cm (range 1.2 to 2.8). Six tumors were in the upper renal pole, 6 were in the mid portion of the kidney and 4 were in the lower pole. We subclassified lesions based on the CT derived percent of tumor that extended into the normal renal parenchymal border as exophytic— greater than 60% in 6 cases, endophytic—less than 40% in 4 and mesophytic— 40% to 60% in 5. Average tumor incursion in the 3 groups was 7.8 (range 5 to 10), 13.6 (range 10 to 17) and 10.6 mm (range 6 to 15), respectively. No tumors were completely intraparenchymal. Statistical analysis for comparing the transperitoneal (TP) and retroperitoneal (RP) groups was performed using the Student t test. All tests were 2-tailed with statistical significance considered at p ⬍0.05. One patient with bilateral lesions was excluded from analysis of operative time and change in serum creatinine (Cr). TECHNIQUE
Depending on tumor location the TP approach for anterior directed lesions or the RP approach for posterior directed lesions was used. No external or internal ureteral stent was placed. Renal hilar clamping was done in 1 patient with a
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history of bleeding diathesis in whom preoperative coagulation parameters were normal. After dissecting the overlying Gerota’s fascia and fat the tumor periphery was scored using hook electrocautery and the ABC (part B of figure). At 20 to 25 mm Hg pneumoperitoneum the initial circumferential incision was then extended with harmonic shears to a depth that was believed to be just below the medial extent of the tumor, as measured on CT. The parenchyma underlying the tumor was then incised, thereby, freeing the tumor from the kidney. Pneumoperitoneum was then decreased to 15 mm Hg. The specimen was sent for frozen section. Hemostasis was achieved using the ABC (part C of figure). Tisseel was then generously applied to the resection bed, followed by a layer of oxidized, regenerated cellulose. Another layer of Tisseel was
TABLE 1. Patient demographics No. pts Mean age (range) No. men/women Mean body mass index (range) Mean American Society of Anesthesiologists score (range) Mean cm CT tumor size (range)
15 68 (53–83) 12/3 29.5 (23–59) 2.4 (2–4) 2.2 ⫻ 2.2 (1.4–2.8 ⫻ 1.2–2.7)
then applied (part D of figure). In 5 cases the Tissuelink device (TissueLink, Dover, New Hampshire) was used in conjunction with the ABC. However, the operating surgeon did not rely on it for hemostasis and still applied the described hemostatic sandwich. A 5 mm Blake drain was placed via the most lateral port site. RESULTS
Mean operative time was 3.8 hours (range 3.0 to 5.0) (table 2). Mean blood loss was 108 ml (range 20 to 300) (table 3). The mean difference between preoperative and postoperative (hospital discharge) hemoglobin (Hb) and hematocrit (Hct) was 2.77 gm/dl (range 1.1 to 4.6, p ⬍0.001, normal 11.5 to 15) and 8.5% (range 1.7% to 12.3%, p ⬍0.001, normal 34% to 44%), respectively. None of the patients required transfusion. Nine cases were approached retroperitoneally and 6 were approached transperitoneally. One patient underwent intraoperative conversion from the RP to the TP approach. In the patient who required renal arterial clamping clamp time was 18 minutes. Serum creatinine was 0.9 mg/dl preoperatively and 0.8 mg/dl at discharge home (normal 0.5 to 1.3). Overall the mean difference in preoperative and discharge creatinine in unclamped LWR cases was 0.05 mg/dl (range ⫺0.2 to 0.3, p ⫽ 0.31). Mean long-term (greater than 30-day) creatinine was 1.11 mg/dl (range 0.7 to 2.2). The patient with a long-
RP approach to laparoscopic excision of exophytic renal mass. A, CT reveals right 3.5 ⫻ 3.2 cm middle posterior peripheral exophytic mass 75% above kidney surface. B, intraoperative photograph shows right renal mass after being exposed. Some peri-mass fat was already sent for histopathology but fat tag remains on lesion surface. C, mass is circumferentially scored with ABC. D, after removal of mass and treatment of base with ABC initial layer of fibrin glue is applied, followed by layer of oxidized, regenerated cellulose. View shows second, outer layer of fibrin glue being applied.
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FIBRIN GLUE-OXIDI ZED CELLULOSE SANDWICH FOR LAPAROSCOPIC WEDGE RESECTION TABLE 2. Operative and pathological data No. approach (%): RP TP Mean operative time (mins) No. renal hilar clamping Mean clamp time (mins) Mean creatinine change (mg/dl)* Mean estimated blood loss (ml) Mean hematocrit change (%)* No. RCC (%): Clear cell Chromophobe Granular Papillary Mixed No. benign masses (%): Oncocytoma Angiomyolipoma Complex cyst Mean tumor size (cm): CT Pathological Mean tumor incursion (mm) Mean margin (mm) * Preoperative ⫺ hospital discharge value.
Overall
Endophytic
Exophytic
Mesophytic
9 (56) 7 (44) 229 1 18 0.05 108 8.5 10 (67) 7 1 0 1 1 5 (33) 3 1 1
3 1 225 0 0 0.03 150 11.0
2 4 232 1 18 0.07 121 8.7
4 2 227 0 0 0.04 93 6.9
2 0 0 0 0
4 0 0 1 0
1 1 0 0 1
2 0 0
1 0 0
0 1 1
2.2 ⫻ 2.2 2.1 ⫻ 1.8 10.7 3.2
2.0 ⫻ 2.0 2.3 ⫻ 1.9 13.6 2.8
TABLE 3. Preoperative and postoperative data by tumor class Overall Endophytic Exophytic Mesophytic Mean preop: Cr (mg/dl) 0.98 1.17 1.08 0.86 Hb (gm/dl) 13.8 13.5 14.2 13.5 % Hct 40.7 39.8 42.4 40.0 Mean postop:* Cr (mg/dl) 1.03 1.20 1.08 0.86 Hb (gm/dl) 11.0 10.2 11.5 11.2 % Hct 32.5 29.7 33.7 33.1 Cr change (mg/dl) 0.05 0.03 0.07 0.04 Hb change (gm/dl) 2.77 3.6 2.7 2.3 % Hct change 8.5 11.0 8.7 6.9 Greater than 1 mo Cr 1.11 1.43 1.02 0.93 (mg/dl)† * Hospital discharge values (change ⫽ preoperative ⫺ postoperative value). † Range 0.7 to 2.2 mg/dl, preoperative value 1.7 to 2.8 gm/dl.
term creatinine of 2.2 mg/dl had renal insufficiency preoperatively (creatinine range 1.7 to 2.8 mg/dl). Mean postoperative narcotic use was 17.3 mg morphine sulfate equivalents (range 2 to 30.2). There were no significant differences in hospital stay (3.0 vs 2.3 days, p ⫽ 0.17), operative time (237 vs 225 minutes, p ⫽ 0.72), estimated blood loss (90.6 vs 143.8 ml, p ⫽ 0.69) or postoperative narcotic use (16.0 vs 19.9 mg, p ⫽ 0.54) between the RP and TP groups. The mean change in hemoglobin and hematocrit in the RP and TP groups was 2.6 vs 2.8 gm/dl and 8.1% vs 9.6%, respectively. The mean difference in preoperative and hospital discharge creatinine between the groups was 0.1 vs 0.05 mg/dl (p ⫽ 0.18). The change (preoperative ⫺ hospital discharge value) in hemoglobin in the endophytic, exophytic and mesophytic groups was 3.6, 2.7 and 2.3 gm/dl, respectively. The change in hematocrit in the 3 groups was 11.0%, 8.7% and 6.9%, respectively. The mean change in creatinine was 0.03, 0.07 and 0.04 mg/dl, respectively (table 3). Mean estimated blood loss in each group was 150, 121 and 93 ml, respectively. Mean operative time was 225, 232 and 227 minutes, respectively. Histological examination revealed 10 renal cell carcinoma (RCC) cases (67%), including clear cell in 7, papillary in 1, mixed (clear/granular) in 1 and chromophobe in 1. Eight lesions were Furhman grades 1 to 2 and 2 lesions were grade 3. The remaining 5 lesions were benign, including 3 oncocytomas, 1 angiomyolipoma and 1 fibrotic cyst. Mean tumor size on pathological examination was 2.1 ⫻ 1.8 ⫻ 1.0 cm
2.5 ⫻ 2.4 2.2 ⫻ 1.7 7.8 3.8
2.2 ⫻ 1.9 1.8 ⫻ 1.8 10.6 2.5
(range 1.1 to 3.5). Margin status was negative in all cases with a mean thickness of 3.2 mm (range 0.1 to 7). Two patients had a margin thinner than 1 mm, including 1 with grade 1 clear cell RCC and 1 with oncocytoma. Mean hospital stay and time to resumption of oral intake was 2.7 (range 2 to 4) and 1.4 days (range 1 to 2), respectively. Postoperatively 1 patient had a 3.8 ⫻ 5.4 cm asymptomatic perinephric hematoma, which was found on CT after hospital discharge that was done because of a hemoglobin of 7.3 gm/dl at the initial followup visit. The hematoma resolved at subsequent followup without intervention or transfusion. Median followup was 10 months (range 4 to 21). There have been no recurrences to date. DISCUSSION
The management of large renal masses by laparoscopic radical nephrectomy has become the standard of care at most medical centers.1 However, the adoption of laparoscopic nephron sparing surgery has been relatively slow in comparison. The major concern when performing nephron sparing surgery is blood loss. Accordingly open partial nephrectomy is often associated with clamping the renal vessels and then proceeding under warm or cold ischemic conditions. As an alternative to vessel clamping, some groups have used mechanical restriction of arterial blood flow with various devices.2⫺4 Does clamping the renal vessels with warm ischemia result in any impairment of renal function and, if so, at what point do these irreversible changes occur? Acute tubular necrosis is the second most common complication after nephron sparing surgery, occurring in a mean of 6.3% of patients.5 The primary etiology is ischemic renal injury and decreased renal mass. In general based on animal data it is believed that warm ischemia times up to 40 minutes are well tolerated. A more recent report in pigs extends this safe limit up to 90 minutes.6 However, recently, Guillonneau et al compared the mean difference between preoperative and 1 month postoperative serum creatinine after LPN with and without vessel clamping in 28 unmatched patients.7 With an average clamp time of only 27.3 ⫾ 7 minutes (range 15 to 47) he found a change in serum creatinine of 0.42 mg/dl in the clamped group vs 0.04 mg/dl in the unclamped group despite similar size renal lesions in the 2 groups (2.5 vs 2.0 cm). Operative time and estimated blood loss were 121.5 minutes and 270 ml (range 25 to 1,200) in the clamped group, and 179.1 minutes
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and 708 ml (range 200 to 1,800) in the unclamped group, respectively. ABC, fibrin glue, FloSeal (Baxter Corp.) and other hemostatic agents were not used. In the series of Gill et al comparing 100 laparoscopic and 100 open nephron sparing procedures vascular clamping was performed in 97% of cases in the laparoscopic group with an average warm ischemia time of 27.8 minutes.8 Although the reported change in creatinine was minimal (0.10 mg/dl), in a subset of 7 patients with LWR or LPN and a solitary kidney the change in creatinine was 0.50 mg/dl. The argument for clamping may soon become moot if newer instrumentation can achieve the goal of bloodless parenchymal dissection. To this end a high pressure water jet dissector (Helix Hydro-Jet, Erbe, Tu¨bingen, Germany) has been successfully used in animals.9 Clinical laparoscopic applications are still pending. Another device, the holmium: YAG laser, has also been used for parenchymal resection during LPN.10 However, in this report of 3 patients estimated blood loss was 50 to 500 ml. Finally and most promisingly, Yoshimura et al used a microwave tissue coagulator (Microtaze OT-110-M, Heiwa Electronics Industry, Tokyo, Japan) combined with sharp tissue dissection in 6 patients.11 Blood loss was less than 50 ml. However, all of these series comprise a small clinical experience with short followup. Various topical hemostatics and sealants have been developed. Older materials include oxidized, regenerated cellulose, such as Surgicel and Gelfoam (Pharmacia and Upjohn, Kalamazoo, Michigan). Newer agents such as gelatin matrix hemostatic sealant (FloSeal) contain a viscous collagen matrix combined with concentrated human thrombin that requires active bleeding to work. Fibrin glues such as Tisseel and Cross-seal (American Red Cross Plasma Services, Arlington, Virginia) contain human thrombin and fibrinogen in separate syringes that are simultaneously injected at the desired site of action. The compound forms a stable adherent clot that seals small leaks and promotes hemostasis. Coseal (Baxter Corp.) is another sealant of which the mechanism of action depends on host coagulation factors. It contains 2 polyethylene glycol polymers that combine to form a covalenty bonded gel. Patel et al used a fibrin sealant (Hemaseel, Hemacure, Montreal, Quebec, Canada) in conjunction with Gelfoam to seal 3 to 5 and 10 mm collecting system defects during open and hand assisted laparoscopic porcine LWR and LPN, respectively.12 No sutures were placed. No leaks were observed at physiological collecting system pressures regardless of the size of the collecting system defect. Mean leak point pressure was supraphysiological at 66 cm H2O (range 50 to 80). In our patients following initial hemostasis with the ABC hemostasis is reinforced by constructing a Tisseel-SurgicelTisseel sandwich. Our approach is similar to that described by Wolf et al using a hand assisted approach.13 In their series of 39 patients only 1 had postoperative urine leakage, which was successfully treated with an indwelling stent. At least in the early followup period LWR and LPN appear to prevent tumor recurrence at least as well as open resection. The reported recurrence rate of wedge excision is 2.3% to 5.4% for lesions less than 4.0 cm at a followup out to 4 years.14, 15 In the current series followup is brief at only 10 months. At this time with surgical margins of 0.1 to 7 mm no local recurrences were observed. Of note, all of our patients also underwent complete ABC treatment of the renal bed. The depth of penetration of ABC is 2 to 3 mm, thereby, perhaps providing an additional in situ surgical margin beyond the noted histological margin. The minimum clear margin necessary after resection of renal cancers now appears to be 2.5 to 5 mm or less rather than the traditional 10 mm. Li et al sectioned 82 kidneys with small renal cell carcinoma at 3 mm intervals.16 Mean tumor size was 3.4 ⫾ 0.7 cm (range 1.5 to 4.0). They applied immunohistochemistry to renal parenchyma beyond the tu-
mor to detect microscopic tumor extension. Of 82 lesions 12 penetrated the pseudocapsule and 4 had satellites. The average distance beyond the pseudocapsule of each lesion type was 4.5 mm (range 1 to 20). Thus, they recommended a minimum resection margin of 5 mm beyond the visible tumor. Indeed, according to this series the chance of tumor recurrence when the margin is at least 2.5 mm is only 3.7%. Similarly Sutherland et al analyzed recurrence rates and surgical margin size after partial nephrectomy for T1– 2N0M0 RCC in 41 patients.17 They found 2 local recurrences (4.8%) at a mean followup of 4 years in patients with an average negative surgical margin of 2.5 mm (range 0.5 to 7). However, small, low grade renal cell cancers may require far more than 4 years to grow to a radiographically detectable size, given the reported average growth rate for renal cell carcinoma of 0.1 to 0.36 cm yearly.18, 19 Zucchi et al evaluated the incidence of satellite lesions after partial nephrectomy with 10 mm margins in 63 cases of renal cell carcinoma.20 They found only 4 satellite lesions (6%), which were an average of 5.3 mm from the primary lesion. For small RCCs, while enucleation is to be eschewed, minimal margins of 2.5 to 5 mm of normal renal parenchyma appear adequate to prevent local tumor recurrence and enable maximal nephron sparing. Given that the need for a 10 mm margin no longer exists, many nonhilar, nonendophytic renal tumors can be excised without the need for inducing generalized renal ischemia. Similarly with tighter margins the need to enter the collecting system is also decreased, while a greater amount of normally functioning renal parenchyma is preserved. This approach becomes even more appealing in the laparoscopic environment because pneumoperitoneum helps decrease venous bleeding, while advances in technology have now provided the urologist with an unprecedented armamentarium for controlling renal parenchymal bleeding. Accordingly for nonhilar surface visible lesions extending less than 10 mm into the renal parenchyma we believe that hilar dissection and hilar clamping are not necessary. Lastly, it must be noted that not all renal masses are created equal. As such, we found interesting differences when renal masses were separated into an exophytic group— greater than 60% of the lesion off of the renal surface, a mesophytic group— 40% to 60% of the lesion off of the renal surface and an endophytic group—less than 40% of the lesion off of the renal surface. Exophytic and mesophytic lesions, which comprised 75% of the renal masses in our series, are most amenable to excision without vascular control. This information is readily available from preoperative spiral CT with 3-dimensional reconstruction. For lesions that are endophytic or hilar, hilar dissection and vessel clamping are planned, whereas for exophytic and mesophytic lesions 10 mm or less into the renal parenchyma a nonischemic approach is used. CONCLUSIONS
Our technique of using the harmonic shears and ABC in combination with a hemostatic sandwich during laparoscopic wedge excision markedly limits the need for vascular clamping when treating nonhilar, nonendophytic renal lesions. We believe that if the goals of surgery are cure and the preservation of maximal renal function, the approach should be one of tighter margins and the selective use of warm ischemia. These goals are now more readily achievable. The age of surgical pharmaceuticals has arrived. REFERENCES
1. Zisman, A., Pantuck, A. J., Belldegrun, A. S. and Schulam, P. G.: Laparoscopic radical nephrectomy. Semin Urol Oncol, 19: 114, 2001 2. Cadeddu, J. A. and Corwin, T. S.: Cable tie compression to
FIBRIN GLUE-OXIDI ZED CELLULOSE SANDWICH FOR LAPAROSCOPIC WEDGE RESECTION
3. 4.
5. 6.
7.
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9. 10. 11.
facilitate laparoscopic partial nephrectomy. J Urol, 165: 177, 2001 Beck, S. D., Lifshitz, D. A., Cheng, L., Lingerman, J. E. and Shalhav, A. L.: Endoloop-assisted laparoscopic partial nephrectomy. J Endourol, 16: 175, 2002 Gill, I. S., Desai, M. M., Kaouk, J. H., Meraney, A. M., Murphy, D. P., Sung, G. T. et al: Laparoscopic partial nephrectomy for renal tumor: duplicating open surgical techniques. J Urol, 167: 469, 2002 Uzzo, R. G. and Novick, A. C.: Nephron sparing surgery for renal tumors: indication, techniques and outcomes. J Urol, 166: 6, 2001 Maynes, L. J., Berger, K. A., Desai, P. J., Zuppan, C., Winkielman, A., Sterling, T. et al: Determination of the maximum safe laparoscopic warm renal ischemia time in the porcine solitary kidney model. J Urol, suppl., 171: 129, abstract 484, 2004 Guillonneau, B., Bermu´dez, H., Gholami, S., El Fettouh, H., Gupta, R., Adorno-Rosa, J. et al: Laparoscopic partial nephrectomy for renal tumor: single center experience comparing clamping and no clamping techniques of the renal vasculature. J Urol, 169: 483, 2003 Gill, I. S., Matin, S. F., Desai, M. M., Kaouk, J. H., Steinberg, A., Mascha E. et al: Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumors in 200 patients. J Urol, 170: 64, 2003 Shekkariz, B., Upadhyay, J. and Jewett, M.: Further experience with hydro-jet dissection for renal sparing surgery. J Endourol, 16: A24, 2002 Lotan, Y., Gettman, M. T., Ogan, K., Baker, L. A. and Cadeddu, J. A.: Clinical use of the holmium: YAG laser in laparoscopic partial nephrectomy. J Endourol, 16: 289, 2002 Yoshimura, K., Okubo, K., Ichioka, K., Terada, N., Matsuta, Y. and Arai, Y.: Laparoscopic partial nephrectomy with a microwave tissue coagulator for small renal tumor. J Urol, 165: 1893, 2001
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12. Patel, R., Caruso, R. P., Taneja, S. and Stifelman, M.: Use of fibrin glue and gelfoam to repair collecting system injuries in a porcine model: implications for the technique of laparoscopic partial nephrectomy. J Endourol, 17: 799, 2003 13. Wolf, J. S., Jr., Seifman, B. D. and Montie, J. E.: Nephron sparing surgery for suspected malignancy: open surgery compared to laparoscopy with selective use of hand assistance. J Urol, 163: 1659, 2000 14. Hafez, K. S., Fergany, A. F. and Novick, A. C.: Nephron sparing surgery for localized renal cell carcinoma: impact of tumor size on patient survival, tumor recurrence and TNM staging. J Urol, 162: 1930, 1999 15. Lau, W. K., Blute, M. L., Weaver, A. L., Torres, V. E. and Zincke, H.: Matched comparison of radical nephrectomy vs nephronsparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc, 75: 1236, 2000 16. Li, Q. L., Guan, H. W., Zhang, L. Z., Zhang, Q. P., Wang, F. P. and Liu, Y. J.: Optimal margin in nephron-sparing surgery for renal cell carcinoma 4 cm or less in diameter. Eur Urol, 44: 448, 2003 17. Sutherland, S. E., Resnick, M. I., MacLennan, G. T. and Goldman, H. B.: Does the size of the surgical margin in partial nephrectomy for renal cell cancer really matter? J Urol, 167: 61, 2002 18. Volpe, A., Panzarella, T., Rendon, R. A., Haider, M. A., Kondylis, F. I. and Jewett, M. A.: The natural history of incidentally detected small renal masses. Cancer, 100: 738, 2004 19. Bosniak, M. A., Birnbaum, B. A., Krinsky, G. A. and Waisman, J.: Small renal parenchymal neoplasms: further observations on growth. Radiology, 197: 589, 1995 20. Zucchi, A., Mearini, L., Mearini, E., Costantini, E., Vivacqua, C. and Porena, M.: Renal cell carcinoma: histological findings on surgical margins after nephron sparing surgery. J Urol, 169: 905, 2003
Vol. 173, 1477–1481, May 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000154165.12738.7f
Oncology: Renal/Upper Tract/Bladder FIBRIN GLUE-OXIDIZED CELLULOSE SANDWICH FOR LAPAROSCOPIC WEDGE RESECTION OF SMALL RENAL LESIONS DAVID S. FINLEY, DAVID I. LEE, LOUIS EICHEL, CARLOS A. URIBE, ELSPETH M. MCDOUGALL* , AND RALPH V. CLAYMAN† ‡ From the Department of Urology, University of California-Irvine, Orange, California
ABSTRACT
Purpose: We present our experience with standard laparoscopic wedge resection of small renal tumors using a fibrin glue-oxidized cellulose sandwich for hemostasis. Materials and Methods: From May 2002 to December 2003, 15 patients underwent laparoscopic wedge resection for a total of 15 nonhilar renal masses. Renal hilar clamping was performed in 1 patient and no sutures were placed. We used ultrasonic shears and an argon beam coagulator to resect and then coagulate the tumor bed. Tisseel (Baxter Corp., Deerfield, Illinois) was applied to the resection bed, followed by a layer of oxidized, regenerated cellulose (Surgicel, Ethicon, Somerville, New Jersey) and a final layer of Tisseel. Results: Mean preoperative tumor size was 2.2 ⫻ 2.2 ⫻ 2.1 cm. Lesions were subdivided based on the percent of the lesion that extended beyond the renal parenchymal border on computerized tomography as exophytic— greater than 60% in 6 cases, endophytic—less than 40% in 4 and mesophytic— 40% to 60% in 5. Mean operative time was 3.8 hours (range 3 to 5). Mean blood loss was 108 ml (range 20 to 300). No patient required blood transfusion. There was no significant difference in blood loss or change in creatinine among the endophytic, exophytic and mesophytic groups (150, 121 and 93 ml, and 0.03, 0.07 and 0.04 mg/dl, respectively). Margin status was negative in all cases (mean thickness 3.2 mm). Average hospital stay and time to the resumption of oral intake were 2.7 and 1.4 days, respectively. Conclusions: Small exophytic or mesophytic renal lesions can be safely excised laparoscopically without vessel clamping. Excellent hemostasis was achieved in each case with the newer hemostatic agents. KEY WORDS: kidney; carcinoma, renal cell; laparoscopy; nephrectomy; nephrons
Current minimally invasive nephron sparing techniques for small renal masses include laparoscopic partial nephrectomy (LPN) and laparoscopic wedge resection (LWR). Renal parenchymal hemostasis before and during dissection has been achieved using the classic open techniques of renal vascular clamping, hand assisted vascular/parenchymal control and intracorporeal suturing. However, the advent of newer forms of hemostatic instrumentation and agents may simplify the approach. At our hospital we have successfully used the ultrasonic shears and argon beam coagulator (ABC), followed by topical application of a Tisseel-Surgicel sandwich to achieve sutureless hemostasis during LWR for small renal masses. MATERIALS AND METHODS
From May 2002 to December 2003, 12 male and 3 female patients with an average age of 68 years (range 53 to 83), a Submitted for publication July 13, 2004. * Financial interest and/or other relationship with Applied Medical Resources, Yamanouchi Pharma America, Intuitive Surgical, Storz Endoscopy America, Ethicon Endo-Surgery and Simbionix. † Financial interest and/or other relationship with Applied Medical, Endocare, Greenwald, Microvasive, Cook Urological, Orthopedic Systems, Yamanouchi Pharma, Simbionix, Intuitive Surgical, Ethicon Endo-Surgery and Storz Endoscopy. ‡ Correspondence: Department of Urology, University of California, Irvine Medical Center, 101 The City Dr., Building 55, Room 304, Orange, California 92868 (telephone: 714-456-3330; FAX: 714-4565062; e-mail: [email protected]).
mean American Society of Anesthesiologists score of 2.4 (range 2 to 4) and nonhilar cT1N0M0 enhancing renal lesions underwent LWR for a total of 15 renal masses (table 1, part A of figure). Mean computerized tomography (CT) tumor size was 2.2 ⫻ 2.2 cm (range 1.2 to 2.8). Six tumors were in the upper renal pole, 6 were in the mid portion of the kidney and 4 were in the lower pole. We subclassified lesions based on the CT derived percent of tumor that extended into the normal renal parenchymal border as exophytic— greater than 60% in 6 cases, endophytic—less than 40% in 4 and mesophytic— 40% to 60% in 5. Average tumor incursion in the 3 groups was 7.8 (range 5 to 10), 13.6 (range 10 to 17) and 10.6 mm (range 6 to 15), respectively. No tumors were completely intraparenchymal. Statistical analysis for comparing the transperitoneal (TP) and retroperitoneal (RP) groups was performed using the Student t test. All tests were 2-tailed with statistical significance considered at p ⬍0.05. One patient with bilateral lesions was excluded from analysis of operative time and change in serum creatinine (Cr). TECHNIQUE
Depending on tumor location the TP approach for anterior directed lesions or the RP approach for posterior directed lesions was used. No external or internal ureteral stent was placed. Renal hilar clamping was done in 1 patient with a
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history of bleeding diathesis in whom preoperative coagulation parameters were normal. After dissecting the overlying Gerota’s fascia and fat the tumor periphery was scored using hook electrocautery and the ABC (part B of figure). At 20 to 25 mm Hg pneumoperitoneum the initial circumferential incision was then extended with harmonic shears to a depth that was believed to be just below the medial extent of the tumor, as measured on CT. The parenchyma underlying the tumor was then incised, thereby, freeing the tumor from the kidney. Pneumoperitoneum was then decreased to 15 mm Hg. The specimen was sent for frozen section. Hemostasis was achieved using the ABC (part C of figure). Tisseel was then generously applied to the resection bed, followed by a layer of oxidized, regenerated cellulose. Another layer of Tisseel was
TABLE 1. Patient demographics No. pts Mean age (range) No. men/women Mean body mass index (range) Mean American Society of Anesthesiologists score (range) Mean cm CT tumor size (range)
15 68 (53–83) 12/3 29.5 (23–59) 2.4 (2–4) 2.2 ⫻ 2.2 (1.4–2.8 ⫻ 1.2–2.7)
then applied (part D of figure). In 5 cases the Tissuelink device (TissueLink, Dover, New Hampshire) was used in conjunction with the ABC. However, the operating surgeon did not rely on it for hemostasis and still applied the described hemostatic sandwich. A 5 mm Blake drain was placed via the most lateral port site. RESULTS
Mean operative time was 3.8 hours (range 3.0 to 5.0) (table 2). Mean blood loss was 108 ml (range 20 to 300) (table 3). The mean difference between preoperative and postoperative (hospital discharge) hemoglobin (Hb) and hematocrit (Hct) was 2.77 gm/dl (range 1.1 to 4.6, p ⬍0.001, normal 11.5 to 15) and 8.5% (range 1.7% to 12.3%, p ⬍0.001, normal 34% to 44%), respectively. None of the patients required transfusion. Nine cases were approached retroperitoneally and 6 were approached transperitoneally. One patient underwent intraoperative conversion from the RP to the TP approach. In the patient who required renal arterial clamping clamp time was 18 minutes. Serum creatinine was 0.9 mg/dl preoperatively and 0.8 mg/dl at discharge home (normal 0.5 to 1.3). Overall the mean difference in preoperative and discharge creatinine in unclamped LWR cases was 0.05 mg/dl (range ⫺0.2 to 0.3, p ⫽ 0.31). Mean long-term (greater than 30-day) creatinine was 1.11 mg/dl (range 0.7 to 2.2). The patient with a long-
RP approach to laparoscopic excision of exophytic renal mass. A, CT reveals right 3.5 ⫻ 3.2 cm middle posterior peripheral exophytic mass 75% above kidney surface. B, intraoperative photograph shows right renal mass after being exposed. Some peri-mass fat was already sent for histopathology but fat tag remains on lesion surface. C, mass is circumferentially scored with ABC. D, after removal of mass and treatment of base with ABC initial layer of fibrin glue is applied, followed by layer of oxidized, regenerated cellulose. View shows second, outer layer of fibrin glue being applied.
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FIBRIN GLUE-OXIDI ZED CELLULOSE SANDWICH FOR LAPAROSCOPIC WEDGE RESECTION TABLE 2. Operative and pathological data No. approach (%): RP TP Mean operative time (mins) No. renal hilar clamping Mean clamp time (mins) Mean creatinine change (mg/dl)* Mean estimated blood loss (ml) Mean hematocrit change (%)* No. RCC (%): Clear cell Chromophobe Granular Papillary Mixed No. benign masses (%): Oncocytoma Angiomyolipoma Complex cyst Mean tumor size (cm): CT Pathological Mean tumor incursion (mm) Mean margin (mm) * Preoperative ⫺ hospital discharge value.
Overall
Endophytic
Exophytic
Mesophytic
9 (56) 7 (44) 229 1 18 0.05 108 8.5 10 (67) 7 1 0 1 1 5 (33) 3 1 1
3 1 225 0 0 0.03 150 11.0
2 4 232 1 18 0.07 121 8.7
4 2 227 0 0 0.04 93 6.9
2 0 0 0 0
4 0 0 1 0
1 1 0 0 1
2 0 0
1 0 0
0 1 1
2.2 ⫻ 2.2 2.1 ⫻ 1.8 10.7 3.2
2.0 ⫻ 2.0 2.3 ⫻ 1.9 13.6 2.8
TABLE 3. Preoperative and postoperative data by tumor class Overall Endophytic Exophytic Mesophytic Mean preop: Cr (mg/dl) 0.98 1.17 1.08 0.86 Hb (gm/dl) 13.8 13.5 14.2 13.5 % Hct 40.7 39.8 42.4 40.0 Mean postop:* Cr (mg/dl) 1.03 1.20 1.08 0.86 Hb (gm/dl) 11.0 10.2 11.5 11.2 % Hct 32.5 29.7 33.7 33.1 Cr change (mg/dl) 0.05 0.03 0.07 0.04 Hb change (gm/dl) 2.77 3.6 2.7 2.3 % Hct change 8.5 11.0 8.7 6.9 Greater than 1 mo Cr 1.11 1.43 1.02 0.93 (mg/dl)† * Hospital discharge values (change ⫽ preoperative ⫺ postoperative value). † Range 0.7 to 2.2 mg/dl, preoperative value 1.7 to 2.8 gm/dl.
term creatinine of 2.2 mg/dl had renal insufficiency preoperatively (creatinine range 1.7 to 2.8 mg/dl). Mean postoperative narcotic use was 17.3 mg morphine sulfate equivalents (range 2 to 30.2). There were no significant differences in hospital stay (3.0 vs 2.3 days, p ⫽ 0.17), operative time (237 vs 225 minutes, p ⫽ 0.72), estimated blood loss (90.6 vs 143.8 ml, p ⫽ 0.69) or postoperative narcotic use (16.0 vs 19.9 mg, p ⫽ 0.54) between the RP and TP groups. The mean change in hemoglobin and hematocrit in the RP and TP groups was 2.6 vs 2.8 gm/dl and 8.1% vs 9.6%, respectively. The mean difference in preoperative and hospital discharge creatinine between the groups was 0.1 vs 0.05 mg/dl (p ⫽ 0.18). The change (preoperative ⫺ hospital discharge value) in hemoglobin in the endophytic, exophytic and mesophytic groups was 3.6, 2.7 and 2.3 gm/dl, respectively. The change in hematocrit in the 3 groups was 11.0%, 8.7% and 6.9%, respectively. The mean change in creatinine was 0.03, 0.07 and 0.04 mg/dl, respectively (table 3). Mean estimated blood loss in each group was 150, 121 and 93 ml, respectively. Mean operative time was 225, 232 and 227 minutes, respectively. Histological examination revealed 10 renal cell carcinoma (RCC) cases (67%), including clear cell in 7, papillary in 1, mixed (clear/granular) in 1 and chromophobe in 1. Eight lesions were Furhman grades 1 to 2 and 2 lesions were grade 3. The remaining 5 lesions were benign, including 3 oncocytomas, 1 angiomyolipoma and 1 fibrotic cyst. Mean tumor size on pathological examination was 2.1 ⫻ 1.8 ⫻ 1.0 cm
2.5 ⫻ 2.4 2.2 ⫻ 1.7 7.8 3.8
2.2 ⫻ 1.9 1.8 ⫻ 1.8 10.6 2.5
(range 1.1 to 3.5). Margin status was negative in all cases with a mean thickness of 3.2 mm (range 0.1 to 7). Two patients had a margin thinner than 1 mm, including 1 with grade 1 clear cell RCC and 1 with oncocytoma. Mean hospital stay and time to resumption of oral intake was 2.7 (range 2 to 4) and 1.4 days (range 1 to 2), respectively. Postoperatively 1 patient had a 3.8 ⫻ 5.4 cm asymptomatic perinephric hematoma, which was found on CT after hospital discharge that was done because of a hemoglobin of 7.3 gm/dl at the initial followup visit. The hematoma resolved at subsequent followup without intervention or transfusion. Median followup was 10 months (range 4 to 21). There have been no recurrences to date. DISCUSSION
The management of large renal masses by laparoscopic radical nephrectomy has become the standard of care at most medical centers.1 However, the adoption of laparoscopic nephron sparing surgery has been relatively slow in comparison. The major concern when performing nephron sparing surgery is blood loss. Accordingly open partial nephrectomy is often associated with clamping the renal vessels and then proceeding under warm or cold ischemic conditions. As an alternative to vessel clamping, some groups have used mechanical restriction of arterial blood flow with various devices.2⫺4 Does clamping the renal vessels with warm ischemia result in any impairment of renal function and, if so, at what point do these irreversible changes occur? Acute tubular necrosis is the second most common complication after nephron sparing surgery, occurring in a mean of 6.3% of patients.5 The primary etiology is ischemic renal injury and decreased renal mass. In general based on animal data it is believed that warm ischemia times up to 40 minutes are well tolerated. A more recent report in pigs extends this safe limit up to 90 minutes.6 However, recently, Guillonneau et al compared the mean difference between preoperative and 1 month postoperative serum creatinine after LPN with and without vessel clamping in 28 unmatched patients.7 With an average clamp time of only 27.3 ⫾ 7 minutes (range 15 to 47) he found a change in serum creatinine of 0.42 mg/dl in the clamped group vs 0.04 mg/dl in the unclamped group despite similar size renal lesions in the 2 groups (2.5 vs 2.0 cm). Operative time and estimated blood loss were 121.5 minutes and 270 ml (range 25 to 1,200) in the clamped group, and 179.1 minutes
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FIBRIN GLUE-OXIDI ZED CELLULOSE SANDWICH FOR LAPAROSCOPIC WEDGE RESECTION
and 708 ml (range 200 to 1,800) in the unclamped group, respectively. ABC, fibrin glue, FloSeal (Baxter Corp.) and other hemostatic agents were not used. In the series of Gill et al comparing 100 laparoscopic and 100 open nephron sparing procedures vascular clamping was performed in 97% of cases in the laparoscopic group with an average warm ischemia time of 27.8 minutes.8 Although the reported change in creatinine was minimal (0.10 mg/dl), in a subset of 7 patients with LWR or LPN and a solitary kidney the change in creatinine was 0.50 mg/dl. The argument for clamping may soon become moot if newer instrumentation can achieve the goal of bloodless parenchymal dissection. To this end a high pressure water jet dissector (Helix Hydro-Jet, Erbe, Tu¨bingen, Germany) has been successfully used in animals.9 Clinical laparoscopic applications are still pending. Another device, the holmium: YAG laser, has also been used for parenchymal resection during LPN.10 However, in this report of 3 patients estimated blood loss was 50 to 500 ml. Finally and most promisingly, Yoshimura et al used a microwave tissue coagulator (Microtaze OT-110-M, Heiwa Electronics Industry, Tokyo, Japan) combined with sharp tissue dissection in 6 patients.11 Blood loss was less than 50 ml. However, all of these series comprise a small clinical experience with short followup. Various topical hemostatics and sealants have been developed. Older materials include oxidized, regenerated cellulose, such as Surgicel and Gelfoam (Pharmacia and Upjohn, Kalamazoo, Michigan). Newer agents such as gelatin matrix hemostatic sealant (FloSeal) contain a viscous collagen matrix combined with concentrated human thrombin that requires active bleeding to work. Fibrin glues such as Tisseel and Cross-seal (American Red Cross Plasma Services, Arlington, Virginia) contain human thrombin and fibrinogen in separate syringes that are simultaneously injected at the desired site of action. The compound forms a stable adherent clot that seals small leaks and promotes hemostasis. Coseal (Baxter Corp.) is another sealant of which the mechanism of action depends on host coagulation factors. It contains 2 polyethylene glycol polymers that combine to form a covalenty bonded gel. Patel et al used a fibrin sealant (Hemaseel, Hemacure, Montreal, Quebec, Canada) in conjunction with Gelfoam to seal 3 to 5 and 10 mm collecting system defects during open and hand assisted laparoscopic porcine LWR and LPN, respectively.12 No sutures were placed. No leaks were observed at physiological collecting system pressures regardless of the size of the collecting system defect. Mean leak point pressure was supraphysiological at 66 cm H2O (range 50 to 80). In our patients following initial hemostasis with the ABC hemostasis is reinforced by constructing a Tisseel-SurgicelTisseel sandwich. Our approach is similar to that described by Wolf et al using a hand assisted approach.13 In their series of 39 patients only 1 had postoperative urine leakage, which was successfully treated with an indwelling stent. At least in the early followup period LWR and LPN appear to prevent tumor recurrence at least as well as open resection. The reported recurrence rate of wedge excision is 2.3% to 5.4% for lesions less than 4.0 cm at a followup out to 4 years.14, 15 In the current series followup is brief at only 10 months. At this time with surgical margins of 0.1 to 7 mm no local recurrences were observed. Of note, all of our patients also underwent complete ABC treatment of the renal bed. The depth of penetration of ABC is 2 to 3 mm, thereby, perhaps providing an additional in situ surgical margin beyond the noted histological margin. The minimum clear margin necessary after resection of renal cancers now appears to be 2.5 to 5 mm or less rather than the traditional 10 mm. Li et al sectioned 82 kidneys with small renal cell carcinoma at 3 mm intervals.16 Mean tumor size was 3.4 ⫾ 0.7 cm (range 1.5 to 4.0). They applied immunohistochemistry to renal parenchyma beyond the tu-
mor to detect microscopic tumor extension. Of 82 lesions 12 penetrated the pseudocapsule and 4 had satellites. The average distance beyond the pseudocapsule of each lesion type was 4.5 mm (range 1 to 20). Thus, they recommended a minimum resection margin of 5 mm beyond the visible tumor. Indeed, according to this series the chance of tumor recurrence when the margin is at least 2.5 mm is only 3.7%. Similarly Sutherland et al analyzed recurrence rates and surgical margin size after partial nephrectomy for T1– 2N0M0 RCC in 41 patients.17 They found 2 local recurrences (4.8%) at a mean followup of 4 years in patients with an average negative surgical margin of 2.5 mm (range 0.5 to 7). However, small, low grade renal cell cancers may require far more than 4 years to grow to a radiographically detectable size, given the reported average growth rate for renal cell carcinoma of 0.1 to 0.36 cm yearly.18, 19 Zucchi et al evaluated the incidence of satellite lesions after partial nephrectomy with 10 mm margins in 63 cases of renal cell carcinoma.20 They found only 4 satellite lesions (6%), which were an average of 5.3 mm from the primary lesion. For small RCCs, while enucleation is to be eschewed, minimal margins of 2.5 to 5 mm of normal renal parenchyma appear adequate to prevent local tumor recurrence and enable maximal nephron sparing. Given that the need for a 10 mm margin no longer exists, many nonhilar, nonendophytic renal tumors can be excised without the need for inducing generalized renal ischemia. Similarly with tighter margins the need to enter the collecting system is also decreased, while a greater amount of normally functioning renal parenchyma is preserved. This approach becomes even more appealing in the laparoscopic environment because pneumoperitoneum helps decrease venous bleeding, while advances in technology have now provided the urologist with an unprecedented armamentarium for controlling renal parenchymal bleeding. Accordingly for nonhilar surface visible lesions extending less than 10 mm into the renal parenchyma we believe that hilar dissection and hilar clamping are not necessary. Lastly, it must be noted that not all renal masses are created equal. As such, we found interesting differences when renal masses were separated into an exophytic group— greater than 60% of the lesion off of the renal surface, a mesophytic group— 40% to 60% of the lesion off of the renal surface and an endophytic group—less than 40% of the lesion off of the renal surface. Exophytic and mesophytic lesions, which comprised 75% of the renal masses in our series, are most amenable to excision without vascular control. This information is readily available from preoperative spiral CT with 3-dimensional reconstruction. For lesions that are endophytic or hilar, hilar dissection and vessel clamping are planned, whereas for exophytic and mesophytic lesions 10 mm or less into the renal parenchyma a nonischemic approach is used. CONCLUSIONS
Our technique of using the harmonic shears and ABC in combination with a hemostatic sandwich during laparoscopic wedge excision markedly limits the need for vascular clamping when treating nonhilar, nonendophytic renal lesions. We believe that if the goals of surgery are cure and the preservation of maximal renal function, the approach should be one of tighter margins and the selective use of warm ischemia. These goals are now more readily achievable. The age of surgical pharmaceuticals has arrived. REFERENCES
1. Zisman, A., Pantuck, A. J., Belldegrun, A. S. and Schulam, P. G.: Laparoscopic radical nephrectomy. Semin Urol Oncol, 19: 114, 2001 2. Cadeddu, J. A. and Corwin, T. S.: Cable tie compression to
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