- Email: [email protected]
Initial Experience With Robot Assisted Partial Nephrectomy for Multiple Renal Masses
Initial Experience With Robot Assisted Partial Nephrectomy for Multiple Renal Masses Ronald Boris, Miguel Proano, W. Marston Linehan, Peter A. Pinto and Gennady Bratslavsky* From the Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
Abbreviations and Acronyms eGFR ⫽ estimated glomerular filtration rate Submitted for publication February 4, 2009. Study received institutional review board approval. Supported by the National Institutes of Health, National Cancer Institute, Center for Cancer Research Intramural Research Program. * Correspondence: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Dr., MSC 1107, Building 10, CRC, Room 2W-5942, Bethesda, Maryland 208921107, telephone: 301-496-6353; FAX: 301-4805626; e-mail: [email protected]).
For other articles on a related topic see pages 1582 and 1588.
Purpose: We evaluated the feasibility of performing robot assisted partial nephrectomy in patients with multiple renal masses and examined the results of our initial experiences. Materials and Methods: We reviewed the records of 10 patients with multiple renal masses who underwent attempted robot assisted partial nephrectomy within the last 2 years. Demographic information, and intraoperative, perioperative and renal function outcome data on these patients were reviewed. Results: A total of 24 tumors in 9 patients were removed with robot assistance. There was 1 open conversion with successful completion of partial nephrectomy. Of the patients 70% had a known hereditary renal cancer syndrome and the remainder had multifocal disease with unknown germline genetic alterations. Frozen section from the tumor bed evaluated in 5 of 10 cases was negative. One patient experienced urinary leak postoperatively, which resolved by postoperative day 9 without intervention. Of the 24 robotically resected masses 22 were malignant. Our most recent 3 patients underwent successful partial nephrectomy without hilar clamping, obviating the need for warm ischemia. Overall renal function was unchanged at most recent followup with a minimal decrease in operated kidney differential function. Conclusions: Robot assisted partial nephrectomy for multiple renal masses was feasible in our early experience. Patient selection is paramount for successful minimally invasive surgery. Robot assisted partial nephrectomy without hilar clamping, especially in the hereditary patient population in which repeat ipsilateral partial nephrectomy may be anticipated, appears promising but requires further evaluation. Key Words: kidney, nephrectomy, robotics, kidney neoplasms, genetic diseases
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PARTIAL nephrectomy provides cancer control equal to that of radical nephrectomy in select patients with renal neoplasms.1 Laparoscopic partial nephrectomy was introduced in 1993 and more recently robot assisted partial nephrectomy was described as a minimally invasive alternative to open partial nephrectomy.2,3
Initially introduced to excise small exophytic renal masses, these techniques have evolved into procedures duplicating open surgery, and facilitate the safe and accurate removal of larger and more endophytic lesions.4 However, not much is known about the role of laparoscopy for multifocal renal masses.
0022-5347/09/1824-1280/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 182, 1280-1286, October 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.06.036
ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
The incidence of multifocal disease is 6% to 25% in the sporadic population.5 Multifocality is considerably higher in the hereditary renal cancer population, as in patients with von Hippel-Lindau, hereditary papillary renal carcinoma and Birt-Hogg-Dubé syndrome. Even at high volume centers where groups have laparoscopic expertise the constraints of warm ischemia time needed for resecting multiple tumors typically directs the surgeon toward an open approach. Also, in the hereditary kidney population or in patients with multifocal renal masses the known risk of recurrence or de novo tumor formation is much greater than in the general population. This frequently requires repeat intervention associated with higher morbidity, underscoring our quest toward maximizing tumor removal while minimizing hilar dissection and clamping in the open and laparoscopic settings. We present our initial experience with robot assisted partial nephrectomy for 2 or more ipsilateral renal masses to evaluate the usefulness of minimally invasive surgery for multifocal renal disease.
MATERIALS AND METHODS Between March 2007 and December 2008 we attempted 10 robot assisted partial nephrectomies for multiple tumors in the same renal unit. All patients were evaluated on a protocol approved by the institutional review board. Seven of 10 patients (70%) had known hereditary conditions predisposing to the risk of renal tumors, including 4 with von Hippel-Lindau, 2 with Birt-Hogg-Dubé syndrome and 1 with hereditary papillary renal carcinoma, while the remainder had multifocal disease with unknown germline genetic alteration. Data were obtained from reviews of operative and pathology reports, history and physical examination at hospital admission and discharge, and anesthesia records. Operative data are reported on patients in whom robot assisted partial nephrectomy was evaluated. As previously defined by Finley et al, exophytic tumors were those
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in which the lesion extended more than 60% off the kidney surface, endophytic tumors had less than 40% of the lesion off the kidney surface and mesophytic tumors were between 40% and 60% off the natural kidney border.6 Preoperative evaluation included abdominal and chest imaging, routine laboratory analysis and nuclear renal scan. All studies were repeated at a 3-month followup visit. Functional outcomes were assessed using serum creatinine, 24-hour urine creatinine clearance, eGFR calculated by the modification of diet in renal disease formula equation and mercaptoacetyltriglycine nuclear renogram. Cystoscopy and preplaced ureteral catheter with the patient supine were established in 8 of 10 patients at surgeon discretion in anticipation of collecting system entry. All patients were then placed in the modified flank position with the robot docked over the ipsilateral shoulder. A standard 3-arm da Vinci® Surgical System and a transperitoneal approach were used in all cases. Pneumoperitoneum at 15 mm Hg achieved using a Veress needle was well tolerated by all patients. Five ports were used for left surgery and 6 were placed for right surgery to add a 5 mm liver retractor instrument. Figure 1 shows port placement on the left and right sides for robot assisted partial nephrectomy. The 30-degree down camera lens was used throughout the operation. After colon reflection the kidney was mobilized, and the hilum was identified and partially dissected to allow placement of a laparoscopic bulldog or Satinsky clamp as necessary. Laparoscopic ultrasound guidance was used routinely in each case to define tumor number and extent. Surgical extirpation was begun with smaller exophytic lesions, progressing to larger, deeper tumors. All tumors were resected by a technique previously described for hereditary renal disease at the National Institutes of Health.7 Briefly, the tumor pseudocapsule was identified and a plane was developed between the tumor and the renal parenchyma. The tumor was inspected intracorporeally to ensure an intact pseudocapsule. The resection site base was not routinely cauterized. Permanent or frozen biopsy of the resection base was performed at surgeon discretion. Initially in our experience the hilum was occluded with laparoscopic bulldog or
Figure 1. Port placement. A, left side. B, right side
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ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
Satinsky clamps before resecting the largest tumor. However, more recently hilar occlusion was done only when bleeding from tumor extraction became excessive or limited the ability to see dissection planes. Retrograde injection of diluted methylene blue solution in cases with a preplaced ureteral catheter facilitated potential repair by allowing precise visualization of any collecting system injury, which was closed separately with running 3-zero polyglactin suture. Renorrhaphy was performed using interrupted capsular 2-zero polyglactin sutures preplaced with 10 mm Hem-o-Lok® and Lapra-TY® II clips on 1 end. The defect was filled with Surgicel® cigar-shaped bolsters and hemostatic sealant before using the robot needle driver to slide Hem-o-Lok and Lapra-TY II clips on the opposite end down the suture to the desired tension. When renorrhaphy was complete, the clamps (if used) were removed and the defect was inspected for hemostasis. A 15 mm Jackson-Pratt drain was placed at the completion of all cases.
RESULTS A total of 24 tumors were removed in 9 of the 10 patients. Lesions were on the right side in 7 cases and on the left side in 3. Average followup was 9.4 months (range 0 to 20). Mean patient age was 50 years (range 26 to 69) and 50% of the patients were male. Seven patients (70%) had a known hereditary syndrome. Mean operative time was 257 minutes (range 195 to 330). Six of 9 patients (66%) required hilar clamping with a mean ischemia time of 19.7 minutes (range 0 to 48), including the off clamp cohort. Median warm ischemia time in cases with clamping was 29.6 minutes (range 19 to 48). Mean ischemia time per tumor resected in the entire cohort was 7.4 minutes and per tumor resected in patients with hilar ischemia it was 11.1 minutes. Ischemia time per tumor was calculated by dividing total warm ischemia time by the total number of tumors removed. Mean intraoperative blood loss was 360 cc (range 100 to 500) and no patient required blood transfusion. All patients had at least 2 or more tumors removed (mean 2.7, range 2 to 4). Mean tumor size was 2.3 cm (range 0.5 to 5.5). Frozen section of the base, which was done in 5 of 10 patients, was negative. There were no renal unit losses. One conversion to open surgery occurred early in the procedure secondary to bleeding. The decision was made to avoid hilar clamping early before resecting larger, deeper masses. Therefore, the case was converted to open partial nephrectomy with 8 tumors resected. There were no intraoperative complications in our series. One case of urinary leak was managed expectantly with extended Jackson-Pratt drainage. The patient did not require ureteral stenting and the leak resolved by postoperative day 9. Average length of stay was 4 days (range 2 to 6).
Table 1 lists tumor pathology, number, size, location and depth, and ischemia. Of removed lesions 75% were endophytic and the remaining 25% were divided evenly between mesophytic and exophytic tumors. Of the 24 resected tumors 22 (92%) were malignant on final pathological evaluation. Table 2 lists renal function outcomes. Total operated kidney eGFR and differential function were decreased an average of 5 ml per minute and 6.5%, respectively.
DISCUSSION Hereditary kidney cancer differs from sporadic cases in that tumors are more frequently bilateral and multifocal, and occur at an earlier age.8 Historically patients with hereditary renal disease are closely monitored and progress to surgery when the largest tumor is 3 cm.7 This patient population represents an absolute indication for nephron sparing surgery due to the high tumor recurrence rate, need for repeat partial nephrectomy and risk of long-term renal replacement therapy. Nephron preservation is especially important in patients who present with multifocal ipsilateral disease since they are at 5 times greater risk for contralateral recurrence than patients with a unilateral renal mass.9 Whether partial nephrectomy is performed using an open or a laparoscopic approach, the goals of surgery remain identical, that is oncological efficacy, renal preservation and early convalescence. Although initially only small, solitary, exophytic tumors were selected for laparoscopic removal, refinements in laparoscopic technique and the recent introduction of robot assisted surgery have facilitated a minimally invasive approach for more complex renal masses.4 We performed partial nephrectomy with resection of up to 4 tumors from a single renal unit using robot assistance. Several observations support robot use for these complex surgeries. 1) While solitary tumors in the sporadic population typically require a 1 to 5 mm surgical margin of normal parenchyma, our patient cohort is typically treated with tumor resection by maintaining the plane between the normal renal parenchyma and the tumor pseudocapsule. This technique was previously described and used for many years in our open series, providing excellent oncological outcomes.7 Adding the robot wristed articulation facilitates the navigation of these challenging dissection planes, allowing these tumors to be excised safely and precisely. 2) The advantages of pneumoperitoneum may decrease blood loss and allow the potential for off clamp partial nephrectomy, thus mimicking our open technique. In fact, our current results compare favorably in regard to esti-
ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
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Table 1. Tumor characteristics and ischemia use for resection Size (cm)
Pole Site
Depth
% Tumor Outside Renal Cortical Surface
1 2 3
0.8 1.1 2.6
Mid Mid Upper
Endophytic Endophytic Endophytic
0 0 0
Hybrid Hybrid Hybrid
0 0 24
1 2 3 4
1.2 1.3 2.1 2.9
Upper Upper Lower Upper
Endophytic Endophytic Endophytic Exophytic
0 0 10 90
Hybrid Hybrid Hybrid Hybrid
Total 48
1 2
0.8 3.0
Upper Med
Endophytic Endophytic
0 0
Angiomyolipoma Oncocytoma
1 2
0.5 5.5
Med Med
Endophytic Endophytic
0 0
Pap 1 Pap 1
Total 41
1 2 3
1.2 1.6 4.4
Upper Upper Lower
Mesophytic Endophytic Exophytic
50 0 80
Clear Clear Clear
0 0 19
1 2
2.5 3.5
Med Med
Endophytic Endophytic
20 10
Clear Clear
0 0
1 2 3 4
1.0 1.4 2.0 3.6
Med Upper Lower Upper
Endophytic Mesophytic Endophytic Mesophytic
10 50 10 50
Clear Clear Clear Clear
0 0 0 0
1 2
1.1 2.6
Upper Upper
Endophytic Endophytic
0 30
Pap 1 Pap 1
0 20
1 2
3.3 1.8
Upper Med
Endophytic Exophytic
0 80
Hybrid Hybrid
0 9
Pt No. (tumor No.)
Pathological Findings
Warm Ischemia (mins)*
1:
2:
3: 0 26
4:
5:
6:
7:
8:
9:
* Mean 19.7 minutes.
mated blood loss in earlier series of open partial nephrectomy, although the number of tumors resected in earlier series was greater.7 Also, avoiding renal clamping may be beneficial for renal preservation and the prevention of postoperative bleeding by performing tumor resection with immediate repair of bleeding vessels. Also, minimal renal
hilum dissection may decrease some of the vascular complications observed in our repeat and salvage partial nephrectomy series in this patient population.10,11 3) Since 75% of tumors in this series were endophytic, they required precise intracorporeal suturing, which was potentially aided by robot assisted surgery compared with
Table 2. Renal function outcomes Serum Creatinine (mg/dl) Pt No. 1 2 3 4 5 6 7 8 9 Mean
eGFR (ml/mm/1.73 m2)
% Renal Scan
Preop
Postop
Preop
Postop
Preop
Postop
% Differential Function
0.9 0.8 0.8 1.0 0.7 1.0 1.1 0.7 0.8 0.86
0.9 0.8 0.9 1.1 0.8 1.1 1.1 0.6 0.8 0.9
91 128 75 71 101 84 80 144 74 94
91 120 73 65 86 74 80 144 72 89
59 50 57 49 59 50 55 47 50 53
51 46 43 43 53 42 49 47 Not available 47
⫺8 ⫺4 ⫺14 ⫺6 ⫺6 ⫺8 ⫺6 0 Not available ⫺6.5
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traditional laparoscopy. 4) Because many patients in our cohort will require repeat intervention in the future, we anticipate that reoperation after a minimally invasive approach may be technically easier than reoperation after open surgery. Although to our knowledge there are no published data on this subject in the urological literature, bariatric surgeons described a 2-stage laparoscopic approach, lending credence to this argument.12 There are limited published data on minimally invasive surgery for multiple ipsilateral renal masses. Investigators noted a 4.5% incidence of 2 or more detected tumors in the same kidney and treated 13 patients with minimally invasive techniques.13 Only 2 of the 13 patients underwent laparoscopic partial nephrectomy for multiple tumors during the same procedure. In 8 of 13 patients 1 or all tumors were treated with cryotherapy. In a more recent study from the same institution 27 patients with multiple ipsilateral renal tumors were treated with laparoscopic partial nephrectomy or cryoablation with equivalent early oncological and functional outcomes.14 Nevertheless, enthusiasm for applying ablative technologies in patients with multifocal disease and those at risk for recurrence or de novo tumors should probably be approached with caution. A recent retrospective series from Cleveland Clinic described 10 patients with ablative failure after previous cryotherapy or radio frequency ablation, of whom only 2 underwent successful subsequent partial nephrectomy.15 Although there may be a role for ablation in select patients, surgical extirpation for multiple renal masses may provide the best chance for the longest intervention-free interval.16 We hope that robot assistance may decrease morbidity not only during initial surgery but also for the repeat intervention that is frequently needed in the hereditary and multifocal renal disease population. Although to our knowledge our cohort of patients with multifocal disease is unique, comparison of our series to the largest experiences with robot assisted partial nephrectomy in the sporadic population shows similar outcomes. Ho et al reported 20 consecutive cases with an average tumor size of 3 cm, an average warm ischemia time of 21.7 minutes and an average blood loss of 189 ml.17 There were no intraoperative complications and all patients had a solitary lesion removed. Of 20 removed tumors 12 (60%) were exophytic. Benway et al reported on 50 consecutive robot assisted partial nephrectomies for a single tumor with a mean lesion size of 2.5 cm, a mean warm ischemia time of 17.8 minutes and an average blood loss of 140 ml.18 Of removed tumors 34% were benign, the complication rate was 10% and there was 1 positive margin. In contrast, our
cohort with multiple tumors had a higher degree of malignancy (92%) and endophytic locations (75%), while tumor size, warm ischemia time and the complication rate were comparable. Multifocal renal tumors have been reported in 6.5% to 25% of patients undergoing nephrectomy for renal masses and they remain a difficult diagnostic and therapeutic challenge to the urologist.5 A large multi-institutional study in more than 10,000 patients with renal cell carcinoma described multifocality in 54% with bilateral disease in the general population.19 Unfortunately many of these patients undergo radical or even bilateral nephrectomy. At our institution we traditionally treat patients with hereditary renal syndromes and multifocal renal tumors in similar fashion with open partial nephrectomy.7 Justification for our aggressive approach is founded on the patient desire to avoid renal replacement therapy, inconsequential outcomes of renal transplantation and emerging data supporting renal insufficiency as an independent risk factor for cardiovascular disease, hospitalization and all cause mortality.20 Renal function preservation is the first impetus behind performing partial nephrectomy. Initial concerns with minimally invasive techniques for complex partial nephrectomy rest on the foundation that prolonged warm ischemia time may adversely affect renal function. The historical duration of safe warm ischemia was thought to be 30 minutes. However, it was suggested that an ischemia time of 30 to 55 minutes may not be clinically relevant since minimal changes were noted in preoperative and postoperative creatinine in 118 patients undergoing laparoscopic partial nephrectomy.21 All patients had 2 functioning renal units, which may explain these findings. In a study by Desai et al nuclear renal scan revealed that 39 minutes of warm ischemia during laparoscopic partial nephrectomy resulted in 29% decreased function of the operated renal unit.22 The 6.5% decrease in differential function in our series is less than the 29% described by Desai et al, which may be related to shorter mean ischemia time (19.7 minutes vs 39), renogram timing (3 months vs 1) and a different extirpation technique (resection at the pseudocapsule level vs at a healthy margin). Despite these differences the message remains unchanged that decreasing ischemia time is beneficial for renal preservation. While renal hilar occlusion and its accepted effects of warm ischemia are standard practice for minimally invasive nephron sparing surgery, off clamp robot assisted partial nephrectomy may still allow excellent visualization and preservation of the appropriate dissection plane. In our 3 most recent patients we performed precise tumor excision, pel-
ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
Figure 2. Computerized tomography in patient with von HippelLindau. A, preoperative image shows 2 large endophytic renal lesions (arrows). B, usual postoperative changes at 3 months.
vicaliceal suture repair and renal reconstruction without hilar clamping. In these 3 patients a total of 8 tumors were removed successfully, duplicating our open technique. Estimated mean blood loss was 467 vs 314 cc in the group undergoing resection during hilar clamping. Figure 2 shows preoperative and postoperative computerized tomography in a 33year-old patient with von Hippel-Lindau and 2 large endophytic renal masses who underwent successful off clamp robot assisted partial nephrectomy. This operative strategy may potentially avoid the cumulative renal injury that inevitably occurs with prolonged hilar ischemia while still providing the benefits of minimally invasive surgery. The current study has inherent limitations. It is a retrospective study and our sample size is small. Functional and oncological outcomes are not mature. Furthermore, this series represents a highly select group of patients who were offered the option of robot assisted partial nephrectomy. Multiple factors, including tumor location, size and number, renal function and prior interventions, were considered before selecting our surgical approach. In this initial series no patient underwent
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prior ipsilateral renal or adrenal surgery, although we are now evaluating the feasibility of robotic partial nephrectomy after prior ipsilateral surgery. Also, considerable experience of the team with performing these cases via the open or laparoscopic approach contributed to the success of these complex surgeries. The difference in extirpation strategy may have influenced our ability to remove many of these multifocal tumors in a minimally invasive setting, especially those resected without hilar occlusion. Although these results may not necessarily translate to treatment in patients with a single sporadic tumor, they may translate to treating patients with sporadic multifocal tumors without a known familial disorder. Performing partial nephrectomy with a healthy margin in this population may not be feasible or may incur unforgivable ischemic time, resulting in a high likelihood of significant loss of function in the operated renal unit. Regardless of treatment strategy this study provides information on the feasibility and early outcome of robot assisted partial nephrectomy for multifocal tumors in the ipsilateral kidney.
CONCLUSIONS Robot assisted partial nephrectomy for multiple renal masses was safe and feasible in our early experience. Renal function outcome is minimally affected at limited followup in this cohort. Patient selection is paramount to ensuring a successful surgical outcome. Robotic partial nephrectomy without hilar clamping, especially in the young patient with hereditary renal tumors in whom repeat ipsilateral partial nephrectomy may be anticipated, appears promising but requires further evaluation.
REFERENCES 1. Fergany AF, Saad IR, Woo L et al: Open partial nephrectomy for tumor in a solitary kidney: experience with 400 cases. J Urol 2006; 175: 1630. 2. Winfield HN, Donovan JF, Godet AS et al: Laparoscopic partial nephrectomy: initial case report for benign disease. J Endourol 1993; 7: 521. 3. Gettman MT, Blute ML, Chow GK et al: Roboticassisted laparoscopic partial nephrectomy: technique and initial clinical experience with DaVinci robotic system. Urology 2004; 64: 914. 4. Rogers CG, Metwalli A, Blatt AM et al: Robotic partial nephrectomy for renal hilar tumors: a multi-institutional analysis. J Urol 2008; 180: 2353.
5. Baltaci S, Orhan D, Soyupek S et al: Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma. J Urol 2000; 164: 36.
9. Blute ML, Thibault GP, Leibovich BC et al: Multiple ipsilateral renal tumors discovered at planned nephron sparing surgery: importance of tumor histology and risk of metachronous recurrence. J Urol 2003; 170: 760.
6. Finley DS, Lee DI, Eichel L et al: Fibrin glueoxidized cellulose sandwich for laparoscopic wedge resection of small renal lesions. J Urol 2005; 173: 1477.
10. Johnson A, Sudarshan S, Liu J et al: Feasibility and outcomes of repeat partial nephrectomy. J Urol 2008; 180: 89.
7. Herring JC, Enquist EG, Chernoff A et al: Parenchymal sparing surgery in patients with hereditary renal cell carcinoma: 10-year experience. J Urol 2001; 165: 777.
11. Bratslavsky G, Liu JJ, Johnson AD et al: Salvage partial nephrectomy for hereditary renal cancer: feasibility and outcomes. J Urol 2008; 179: 67.
8. Linehan WM, Walther MM and Zbar B: The genetic basis of cancer of the kidney. J Urol 2003; 170: 2163.
12. Peterli R, Wolnerhanssen BK, Peters T et al: Prospective study of a two-stage operative concept in the treatment of morbid obesity: primary lap-band followed if needed by sleeve gastrec-
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tomy with duodenal switch. Obes Surg 2007; 17: 334. 13. Steinberg AP, Kilciler M, Abreu SC et al: Laparoscopic nephron-sparing surgery for two or more ipsilateral renal tumors. Urology 2004; 64: 255. 14. Lin YC, Turna B, Frota R et al: Laparoscopic partial nephrectomy versus laparoscopic cryoablation for multiple ipsilateral renal tumors. Eur Urol 2008; 53: 1210. 15. Nguyen CT, Lane BR, Kaouk JH et al: Surgical salvage of renal cell carcinoma recurrence after thermal ablative therapy. J Urol 2008; 180: 104.
16. Kunkle DA and Uzzo RG: Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer 2008; 113: 2671. 17. Ho H, Schwentner C, Neururer R et al: Roboticassisted laparoscopic partial nephrectomy: surgical technique and clinical outcomes at 1 year. BJU Int 2009; 103: 663. 18. Benway BM, Wang AJ, Cabello JM et al: Robotic partial nephrectomy with sliding-clip renorrhaphy: technique and outcomes. Eur Urol 2009; 55: 592. 19. Klatte T, Wunderlich H, Patard JJ et al: Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an in-
ternational multicentre experience. BJU Int 2007; 100: 21. 20. Go AS, Chertow GM, Fan D et al: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296. 21. Bhayani SB, Rha KH, Pinto PA et al: Laparoscopic partial nephrectomy: effect of warm ischemia on serum creatinine. J Urol 2004; 172: 1264. 22. Desai MM, Gill IS, Ramani AP et al: The impact of warm ischaemia on renal function after laparoscopic partial nephrectomy. BJU Int 2005; 95: 377.
Abbreviations and Acronyms eGFR ⫽ estimated glomerular filtration rate Submitted for publication February 4, 2009. Study received institutional review board approval. Supported by the National Institutes of Health, National Cancer Institute, Center for Cancer Research Intramural Research Program. * Correspondence: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Dr., MSC 1107, Building 10, CRC, Room 2W-5942, Bethesda, Maryland 208921107, telephone: 301-496-6353; FAX: 301-4805626; e-mail: [email protected]).
For other articles on a related topic see pages 1582 and 1588.
Purpose: We evaluated the feasibility of performing robot assisted partial nephrectomy in patients with multiple renal masses and examined the results of our initial experiences. Materials and Methods: We reviewed the records of 10 patients with multiple renal masses who underwent attempted robot assisted partial nephrectomy within the last 2 years. Demographic information, and intraoperative, perioperative and renal function outcome data on these patients were reviewed. Results: A total of 24 tumors in 9 patients were removed with robot assistance. There was 1 open conversion with successful completion of partial nephrectomy. Of the patients 70% had a known hereditary renal cancer syndrome and the remainder had multifocal disease with unknown germline genetic alterations. Frozen section from the tumor bed evaluated in 5 of 10 cases was negative. One patient experienced urinary leak postoperatively, which resolved by postoperative day 9 without intervention. Of the 24 robotically resected masses 22 were malignant. Our most recent 3 patients underwent successful partial nephrectomy without hilar clamping, obviating the need for warm ischemia. Overall renal function was unchanged at most recent followup with a minimal decrease in operated kidney differential function. Conclusions: Robot assisted partial nephrectomy for multiple renal masses was feasible in our early experience. Patient selection is paramount for successful minimally invasive surgery. Robot assisted partial nephrectomy without hilar clamping, especially in the hereditary patient population in which repeat ipsilateral partial nephrectomy may be anticipated, appears promising but requires further evaluation. Key Words: kidney, nephrectomy, robotics, kidney neoplasms, genetic diseases
1280
www.jurology.com
PARTIAL nephrectomy provides cancer control equal to that of radical nephrectomy in select patients with renal neoplasms.1 Laparoscopic partial nephrectomy was introduced in 1993 and more recently robot assisted partial nephrectomy was described as a minimally invasive alternative to open partial nephrectomy.2,3
Initially introduced to excise small exophytic renal masses, these techniques have evolved into procedures duplicating open surgery, and facilitate the safe and accurate removal of larger and more endophytic lesions.4 However, not much is known about the role of laparoscopy for multifocal renal masses.
0022-5347/09/1824-1280/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 182, 1280-1286, October 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.06.036
ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
The incidence of multifocal disease is 6% to 25% in the sporadic population.5 Multifocality is considerably higher in the hereditary renal cancer population, as in patients with von Hippel-Lindau, hereditary papillary renal carcinoma and Birt-Hogg-Dubé syndrome. Even at high volume centers where groups have laparoscopic expertise the constraints of warm ischemia time needed for resecting multiple tumors typically directs the surgeon toward an open approach. Also, in the hereditary kidney population or in patients with multifocal renal masses the known risk of recurrence or de novo tumor formation is much greater than in the general population. This frequently requires repeat intervention associated with higher morbidity, underscoring our quest toward maximizing tumor removal while minimizing hilar dissection and clamping in the open and laparoscopic settings. We present our initial experience with robot assisted partial nephrectomy for 2 or more ipsilateral renal masses to evaluate the usefulness of minimally invasive surgery for multifocal renal disease.
MATERIALS AND METHODS Between March 2007 and December 2008 we attempted 10 robot assisted partial nephrectomies for multiple tumors in the same renal unit. All patients were evaluated on a protocol approved by the institutional review board. Seven of 10 patients (70%) had known hereditary conditions predisposing to the risk of renal tumors, including 4 with von Hippel-Lindau, 2 with Birt-Hogg-Dubé syndrome and 1 with hereditary papillary renal carcinoma, while the remainder had multifocal disease with unknown germline genetic alteration. Data were obtained from reviews of operative and pathology reports, history and physical examination at hospital admission and discharge, and anesthesia records. Operative data are reported on patients in whom robot assisted partial nephrectomy was evaluated. As previously defined by Finley et al, exophytic tumors were those
1281
in which the lesion extended more than 60% off the kidney surface, endophytic tumors had less than 40% of the lesion off the kidney surface and mesophytic tumors were between 40% and 60% off the natural kidney border.6 Preoperative evaluation included abdominal and chest imaging, routine laboratory analysis and nuclear renal scan. All studies were repeated at a 3-month followup visit. Functional outcomes were assessed using serum creatinine, 24-hour urine creatinine clearance, eGFR calculated by the modification of diet in renal disease formula equation and mercaptoacetyltriglycine nuclear renogram. Cystoscopy and preplaced ureteral catheter with the patient supine were established in 8 of 10 patients at surgeon discretion in anticipation of collecting system entry. All patients were then placed in the modified flank position with the robot docked over the ipsilateral shoulder. A standard 3-arm da Vinci® Surgical System and a transperitoneal approach were used in all cases. Pneumoperitoneum at 15 mm Hg achieved using a Veress needle was well tolerated by all patients. Five ports were used for left surgery and 6 were placed for right surgery to add a 5 mm liver retractor instrument. Figure 1 shows port placement on the left and right sides for robot assisted partial nephrectomy. The 30-degree down camera lens was used throughout the operation. After colon reflection the kidney was mobilized, and the hilum was identified and partially dissected to allow placement of a laparoscopic bulldog or Satinsky clamp as necessary. Laparoscopic ultrasound guidance was used routinely in each case to define tumor number and extent. Surgical extirpation was begun with smaller exophytic lesions, progressing to larger, deeper tumors. All tumors were resected by a technique previously described for hereditary renal disease at the National Institutes of Health.7 Briefly, the tumor pseudocapsule was identified and a plane was developed between the tumor and the renal parenchyma. The tumor was inspected intracorporeally to ensure an intact pseudocapsule. The resection site base was not routinely cauterized. Permanent or frozen biopsy of the resection base was performed at surgeon discretion. Initially in our experience the hilum was occluded with laparoscopic bulldog or
Figure 1. Port placement. A, left side. B, right side
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ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
Satinsky clamps before resecting the largest tumor. However, more recently hilar occlusion was done only when bleeding from tumor extraction became excessive or limited the ability to see dissection planes. Retrograde injection of diluted methylene blue solution in cases with a preplaced ureteral catheter facilitated potential repair by allowing precise visualization of any collecting system injury, which was closed separately with running 3-zero polyglactin suture. Renorrhaphy was performed using interrupted capsular 2-zero polyglactin sutures preplaced with 10 mm Hem-o-Lok® and Lapra-TY® II clips on 1 end. The defect was filled with Surgicel® cigar-shaped bolsters and hemostatic sealant before using the robot needle driver to slide Hem-o-Lok and Lapra-TY II clips on the opposite end down the suture to the desired tension. When renorrhaphy was complete, the clamps (if used) were removed and the defect was inspected for hemostasis. A 15 mm Jackson-Pratt drain was placed at the completion of all cases.
RESULTS A total of 24 tumors were removed in 9 of the 10 patients. Lesions were on the right side in 7 cases and on the left side in 3. Average followup was 9.4 months (range 0 to 20). Mean patient age was 50 years (range 26 to 69) and 50% of the patients were male. Seven patients (70%) had a known hereditary syndrome. Mean operative time was 257 minutes (range 195 to 330). Six of 9 patients (66%) required hilar clamping with a mean ischemia time of 19.7 minutes (range 0 to 48), including the off clamp cohort. Median warm ischemia time in cases with clamping was 29.6 minutes (range 19 to 48). Mean ischemia time per tumor resected in the entire cohort was 7.4 minutes and per tumor resected in patients with hilar ischemia it was 11.1 minutes. Ischemia time per tumor was calculated by dividing total warm ischemia time by the total number of tumors removed. Mean intraoperative blood loss was 360 cc (range 100 to 500) and no patient required blood transfusion. All patients had at least 2 or more tumors removed (mean 2.7, range 2 to 4). Mean tumor size was 2.3 cm (range 0.5 to 5.5). Frozen section of the base, which was done in 5 of 10 patients, was negative. There were no renal unit losses. One conversion to open surgery occurred early in the procedure secondary to bleeding. The decision was made to avoid hilar clamping early before resecting larger, deeper masses. Therefore, the case was converted to open partial nephrectomy with 8 tumors resected. There were no intraoperative complications in our series. One case of urinary leak was managed expectantly with extended Jackson-Pratt drainage. The patient did not require ureteral stenting and the leak resolved by postoperative day 9. Average length of stay was 4 days (range 2 to 6).
Table 1 lists tumor pathology, number, size, location and depth, and ischemia. Of removed lesions 75% were endophytic and the remaining 25% were divided evenly between mesophytic and exophytic tumors. Of the 24 resected tumors 22 (92%) were malignant on final pathological evaluation. Table 2 lists renal function outcomes. Total operated kidney eGFR and differential function were decreased an average of 5 ml per minute and 6.5%, respectively.
DISCUSSION Hereditary kidney cancer differs from sporadic cases in that tumors are more frequently bilateral and multifocal, and occur at an earlier age.8 Historically patients with hereditary renal disease are closely monitored and progress to surgery when the largest tumor is 3 cm.7 This patient population represents an absolute indication for nephron sparing surgery due to the high tumor recurrence rate, need for repeat partial nephrectomy and risk of long-term renal replacement therapy. Nephron preservation is especially important in patients who present with multifocal ipsilateral disease since they are at 5 times greater risk for contralateral recurrence than patients with a unilateral renal mass.9 Whether partial nephrectomy is performed using an open or a laparoscopic approach, the goals of surgery remain identical, that is oncological efficacy, renal preservation and early convalescence. Although initially only small, solitary, exophytic tumors were selected for laparoscopic removal, refinements in laparoscopic technique and the recent introduction of robot assisted surgery have facilitated a minimally invasive approach for more complex renal masses.4 We performed partial nephrectomy with resection of up to 4 tumors from a single renal unit using robot assistance. Several observations support robot use for these complex surgeries. 1) While solitary tumors in the sporadic population typically require a 1 to 5 mm surgical margin of normal parenchyma, our patient cohort is typically treated with tumor resection by maintaining the plane between the normal renal parenchyma and the tumor pseudocapsule. This technique was previously described and used for many years in our open series, providing excellent oncological outcomes.7 Adding the robot wristed articulation facilitates the navigation of these challenging dissection planes, allowing these tumors to be excised safely and precisely. 2) The advantages of pneumoperitoneum may decrease blood loss and allow the potential for off clamp partial nephrectomy, thus mimicking our open technique. In fact, our current results compare favorably in regard to esti-
ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
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Table 1. Tumor characteristics and ischemia use for resection Size (cm)
Pole Site
Depth
% Tumor Outside Renal Cortical Surface
1 2 3
0.8 1.1 2.6
Mid Mid Upper
Endophytic Endophytic Endophytic
0 0 0
Hybrid Hybrid Hybrid
0 0 24
1 2 3 4
1.2 1.3 2.1 2.9
Upper Upper Lower Upper
Endophytic Endophytic Endophytic Exophytic
0 0 10 90
Hybrid Hybrid Hybrid Hybrid
Total 48
1 2
0.8 3.0
Upper Med
Endophytic Endophytic
0 0
Angiomyolipoma Oncocytoma
1 2
0.5 5.5
Med Med
Endophytic Endophytic
0 0
Pap 1 Pap 1
Total 41
1 2 3
1.2 1.6 4.4
Upper Upper Lower
Mesophytic Endophytic Exophytic
50 0 80
Clear Clear Clear
0 0 19
1 2
2.5 3.5
Med Med
Endophytic Endophytic
20 10
Clear Clear
0 0
1 2 3 4
1.0 1.4 2.0 3.6
Med Upper Lower Upper
Endophytic Mesophytic Endophytic Mesophytic
10 50 10 50
Clear Clear Clear Clear
0 0 0 0
1 2
1.1 2.6
Upper Upper
Endophytic Endophytic
0 30
Pap 1 Pap 1
0 20
1 2
3.3 1.8
Upper Med
Endophytic Exophytic
0 80
Hybrid Hybrid
0 9
Pt No. (tumor No.)
Pathological Findings
Warm Ischemia (mins)*
1:
2:
3: 0 26
4:
5:
6:
7:
8:
9:
* Mean 19.7 minutes.
mated blood loss in earlier series of open partial nephrectomy, although the number of tumors resected in earlier series was greater.7 Also, avoiding renal clamping may be beneficial for renal preservation and the prevention of postoperative bleeding by performing tumor resection with immediate repair of bleeding vessels. Also, minimal renal
hilum dissection may decrease some of the vascular complications observed in our repeat and salvage partial nephrectomy series in this patient population.10,11 3) Since 75% of tumors in this series were endophytic, they required precise intracorporeal suturing, which was potentially aided by robot assisted surgery compared with
Table 2. Renal function outcomes Serum Creatinine (mg/dl) Pt No. 1 2 3 4 5 6 7 8 9 Mean
eGFR (ml/mm/1.73 m2)
% Renal Scan
Preop
Postop
Preop
Postop
Preop
Postop
% Differential Function
0.9 0.8 0.8 1.0 0.7 1.0 1.1 0.7 0.8 0.86
0.9 0.8 0.9 1.1 0.8 1.1 1.1 0.6 0.8 0.9
91 128 75 71 101 84 80 144 74 94
91 120 73 65 86 74 80 144 72 89
59 50 57 49 59 50 55 47 50 53
51 46 43 43 53 42 49 47 Not available 47
⫺8 ⫺4 ⫺14 ⫺6 ⫺6 ⫺8 ⫺6 0 Not available ⫺6.5
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ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
traditional laparoscopy. 4) Because many patients in our cohort will require repeat intervention in the future, we anticipate that reoperation after a minimally invasive approach may be technically easier than reoperation after open surgery. Although to our knowledge there are no published data on this subject in the urological literature, bariatric surgeons described a 2-stage laparoscopic approach, lending credence to this argument.12 There are limited published data on minimally invasive surgery for multiple ipsilateral renal masses. Investigators noted a 4.5% incidence of 2 or more detected tumors in the same kidney and treated 13 patients with minimally invasive techniques.13 Only 2 of the 13 patients underwent laparoscopic partial nephrectomy for multiple tumors during the same procedure. In 8 of 13 patients 1 or all tumors were treated with cryotherapy. In a more recent study from the same institution 27 patients with multiple ipsilateral renal tumors were treated with laparoscopic partial nephrectomy or cryoablation with equivalent early oncological and functional outcomes.14 Nevertheless, enthusiasm for applying ablative technologies in patients with multifocal disease and those at risk for recurrence or de novo tumors should probably be approached with caution. A recent retrospective series from Cleveland Clinic described 10 patients with ablative failure after previous cryotherapy or radio frequency ablation, of whom only 2 underwent successful subsequent partial nephrectomy.15 Although there may be a role for ablation in select patients, surgical extirpation for multiple renal masses may provide the best chance for the longest intervention-free interval.16 We hope that robot assistance may decrease morbidity not only during initial surgery but also for the repeat intervention that is frequently needed in the hereditary and multifocal renal disease population. Although to our knowledge our cohort of patients with multifocal disease is unique, comparison of our series to the largest experiences with robot assisted partial nephrectomy in the sporadic population shows similar outcomes. Ho et al reported 20 consecutive cases with an average tumor size of 3 cm, an average warm ischemia time of 21.7 minutes and an average blood loss of 189 ml.17 There were no intraoperative complications and all patients had a solitary lesion removed. Of 20 removed tumors 12 (60%) were exophytic. Benway et al reported on 50 consecutive robot assisted partial nephrectomies for a single tumor with a mean lesion size of 2.5 cm, a mean warm ischemia time of 17.8 minutes and an average blood loss of 140 ml.18 Of removed tumors 34% were benign, the complication rate was 10% and there was 1 positive margin. In contrast, our
cohort with multiple tumors had a higher degree of malignancy (92%) and endophytic locations (75%), while tumor size, warm ischemia time and the complication rate were comparable. Multifocal renal tumors have been reported in 6.5% to 25% of patients undergoing nephrectomy for renal masses and they remain a difficult diagnostic and therapeutic challenge to the urologist.5 A large multi-institutional study in more than 10,000 patients with renal cell carcinoma described multifocality in 54% with bilateral disease in the general population.19 Unfortunately many of these patients undergo radical or even bilateral nephrectomy. At our institution we traditionally treat patients with hereditary renal syndromes and multifocal renal tumors in similar fashion with open partial nephrectomy.7 Justification for our aggressive approach is founded on the patient desire to avoid renal replacement therapy, inconsequential outcomes of renal transplantation and emerging data supporting renal insufficiency as an independent risk factor for cardiovascular disease, hospitalization and all cause mortality.20 Renal function preservation is the first impetus behind performing partial nephrectomy. Initial concerns with minimally invasive techniques for complex partial nephrectomy rest on the foundation that prolonged warm ischemia time may adversely affect renal function. The historical duration of safe warm ischemia was thought to be 30 minutes. However, it was suggested that an ischemia time of 30 to 55 minutes may not be clinically relevant since minimal changes were noted in preoperative and postoperative creatinine in 118 patients undergoing laparoscopic partial nephrectomy.21 All patients had 2 functioning renal units, which may explain these findings. In a study by Desai et al nuclear renal scan revealed that 39 minutes of warm ischemia during laparoscopic partial nephrectomy resulted in 29% decreased function of the operated renal unit.22 The 6.5% decrease in differential function in our series is less than the 29% described by Desai et al, which may be related to shorter mean ischemia time (19.7 minutes vs 39), renogram timing (3 months vs 1) and a different extirpation technique (resection at the pseudocapsule level vs at a healthy margin). Despite these differences the message remains unchanged that decreasing ischemia time is beneficial for renal preservation. While renal hilar occlusion and its accepted effects of warm ischemia are standard practice for minimally invasive nephron sparing surgery, off clamp robot assisted partial nephrectomy may still allow excellent visualization and preservation of the appropriate dissection plane. In our 3 most recent patients we performed precise tumor excision, pel-
ROBOT ASSISTED PARTIAL NEPHRECTOMY FOR MULTIPLE RENAL MASSES
Figure 2. Computerized tomography in patient with von HippelLindau. A, preoperative image shows 2 large endophytic renal lesions (arrows). B, usual postoperative changes at 3 months.
vicaliceal suture repair and renal reconstruction without hilar clamping. In these 3 patients a total of 8 tumors were removed successfully, duplicating our open technique. Estimated mean blood loss was 467 vs 314 cc in the group undergoing resection during hilar clamping. Figure 2 shows preoperative and postoperative computerized tomography in a 33year-old patient with von Hippel-Lindau and 2 large endophytic renal masses who underwent successful off clamp robot assisted partial nephrectomy. This operative strategy may potentially avoid the cumulative renal injury that inevitably occurs with prolonged hilar ischemia while still providing the benefits of minimally invasive surgery. The current study has inherent limitations. It is a retrospective study and our sample size is small. Functional and oncological outcomes are not mature. Furthermore, this series represents a highly select group of patients who were offered the option of robot assisted partial nephrectomy. Multiple factors, including tumor location, size and number, renal function and prior interventions, were considered before selecting our surgical approach. In this initial series no patient underwent
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prior ipsilateral renal or adrenal surgery, although we are now evaluating the feasibility of robotic partial nephrectomy after prior ipsilateral surgery. Also, considerable experience of the team with performing these cases via the open or laparoscopic approach contributed to the success of these complex surgeries. The difference in extirpation strategy may have influenced our ability to remove many of these multifocal tumors in a minimally invasive setting, especially those resected without hilar occlusion. Although these results may not necessarily translate to treatment in patients with a single sporadic tumor, they may translate to treating patients with sporadic multifocal tumors without a known familial disorder. Performing partial nephrectomy with a healthy margin in this population may not be feasible or may incur unforgivable ischemic time, resulting in a high likelihood of significant loss of function in the operated renal unit. Regardless of treatment strategy this study provides information on the feasibility and early outcome of robot assisted partial nephrectomy for multifocal tumors in the ipsilateral kidney.
CONCLUSIONS Robot assisted partial nephrectomy for multiple renal masses was safe and feasible in our early experience. Renal function outcome is minimally affected at limited followup in this cohort. Patient selection is paramount to ensuring a successful surgical outcome. Robotic partial nephrectomy without hilar clamping, especially in the young patient with hereditary renal tumors in whom repeat ipsilateral partial nephrectomy may be anticipated, appears promising but requires further evaluation.
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