LAPAROSCOPIC RADICAL NEPHRECTOMY FOR LARGE (GREATER THAN 7 CM, T2) RENAL TUMORS

0022-5347/04/1726-2172/0 Vol. 172, 2172 2176, December 2004 THE JOURNAL OF UROLOGY Printed in U.S.A. Copyright 2004 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000140961.53335.04 LAPAROSCOPIC RADICAL NEPHRECTOMY FOR LARGE (GREATER THAN 7 CM, T2) RENAL TUMORS ANDREW P. STEINBERG, ANTONIO FINELLI, MIHIR M. DESAI, SIDNEY C. ABREU, ANUP P. RAMANI, MASSIMILIANO SPALIVIERO, LISA RYBICKI, JIHAD KAOUK, ANDREW C. NOVICK AND INDERBIR S. GILL* From the Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio ABSTRACT Purpose: Laparoscopic radical nephrectomy has emerged as a standard of care in appropriate candidates with clinical stage T1 renal tumors (7 cm or less). Herein we present our experience with laparoscopic radical nephrectomy for clinical stage T2 tumors (greater than 7 cm). Materials and Methods: Patients undergoing laparoscopic radical nephrectomy between September 1997 and July 2003 were retrospectively subdivided into group 166 with tumor size 7 cm and group 65 with tumor size greater than 7 cm. Also, group was compared with a group of 34 contemporary, comparable patients undergoing open radical nephrectomy for tumor greater than 7 cm (group ). Results: Compared with group, group had younger patients, larger tumors and greater blood loss (100 vs 200 ml) (each p 0.001). Importantly operative time, analgesic requirements, hospital stay, and convalescence and complication rates were comparable. Group and group patients had similar sized tumors (9.2 and 9.9 cm, respectively) but shorter operative time (p 0.03), lesser blood loss (p 0.001), shorter hospital stay (p 0.001) and more rapid convalescence (p 0.02) occurred in. Conclusions: Laparoscopic radical nephrectomy for stage T2 renal masses (greater than 7 cm) is feasible and efficacious. Laparoscopic nephrectomy offers the advantages of decreased blood loss, shorter hospital stay and more rapid recovery over open radical nephrectomy for comparable tumors greater than 7 cm. Although surgical outcomes are comparable with laparoscopic radical nephrectomy for smaller tumors (7 cm or less), adequate laparoscopic experience is necessary before performing radical nephrectomy for large T2 tumors. KEY WORDS: kidney; carcinoma, renal cell; laparoscopy; nephrectomy Since the initial description of laparoscopic radical nephrectomy (LRN) by Clayman et al in 1991, 1 groups at multiple centers have confirmed its technical feasibility, and successful intermediate and long-term oncological outcomes. 2 5 Using the transperitoneal 2, 3 or retroperitoneal 4, 6 laparoscopic approach the aim remains to duplicate the principles of open radical nephrectomy by removing the kidney surrounded by the perinephric fat and enveloping Gerota s fascia with or without concomitant adrenalectomy. With growing experience LRN has become the standard of care at many centers worldwide in select patients with T1 tumors who are not candidates for nephron sparing surgery. To date the literature on LRN has mostly addressed nephrectomy for clinical stage T1 tumors. The role of laparoscopy in the treatment of large renal masses has been indirectly addressed in only a few recent publications 7, 8 and in the setting of cytoreductive surgery. 9, 10 We report our experience with LRN for large (greater than 7 cm, T2) tumors and compare it to LRN for smaller (7 cm or less, T1) tumors and open radical nephrectomy for comparable large (greater than 7 cm, T2) renal tumors. Accepted for publication July 2, 2004. * Correspondence and requests for reprints: Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, A 100, Cleveland Clinic Foundation, 9500 Euclid Ave., 44195, Cleveland, Ohio (telephone: 216-445-1530; FAX: 216-445-7031; e-mail: gilli@ ccf.org). 2172 MATERIALS AND METHODS The records of patients who underwent LRN for suspected renal cell carcinoma (RCC) at our institution between September 1997 and July 2003 were retrospectively reviewed. Data were accrued from a prospectively maintained computerized database and from hospital charts. From this cohort of 355 patients 231 with complete data available were included in this analysis. LRN was performed in 166 patients with tumors 7 cm or less (group ) and in 65 with tumors greater than 7 cm (group ). Additionally, patients in group were compared with a comparable cohort of 34 patients (group ) who have undergone open radical nephrectomy at our institution since February 2000 for tumors greater than 7 cm. Patients with vena caval tumor thrombus, bulky lymphadenopathy or tumors greater than 14 cm were excluded from analysis. LRN in groups and was performed transperitoneally (32% and 38%) or retroperitoneally (68% and 62%, respectively) based on surgeon preference. The laparoscopic techniques used for the transperitoneal or retroperitoneal approach have been described previously. All specimens were removed intact without morcellation. Groups and were compared with study group. Categorical variables were compared with the chi-square test. Continuous variables are shown as median values and compared using the Wilcoxon rank sum test. Correlations between continuous variables were performed using Spearman correlation coefficients.

LAPAROSCOPIC RADICAL NEPHRECTOMY FOR LARGE RENAL TUMORS 2173 RESULTS Table 1 lists baseline demographics. Patients were older in group compared with group (67 vs 59 years, p 0.001). Gender, American Society of Anesthesiology (ASA) score and body mass index (BMI) were similar. Groups and, which were defined by tumor size, expectedly had a significantly different median tumor size (4.5 vs 9.2 cm, p 0.001). However, median tumor size was comparable between groups and (9.2 and 9.9 cm, respectively, p 0.33). On preoperative computerized tomography the groups had a similar incidence of renal vein involvement (7.3% and 3.4%, respectively, p 0.48). Table 2 lists intraoperative data. Operative time was similar among the 3 groups. Although group had greater estimated blood loss (EBL) compared with group (200 vs 100 ml, p 0.001), the 2 laparoscopic groups had less blood loss than the open group (500 ml, p 0.001). There were 2 open conversions in group and none in group (p 0.51). The 2 open conversions were due to a splenic tear requiring splenectomy and renal arterial bleeding due to clip dislodgment, respectively. Postoperatively the recovery profile was similar in groups and. However, in comparison with group, patients in group had decreased analgesic requirements (p 0.001) and more rapid convalescence (p 0.02, table 2). Although the incidence of intraoperative complications in laparoscopic groups and (7.2% and 7.7%, respectively, p 0.90) was somewhat lower than in group (17.6%), this difference did not achieve statistical significance (p 0.12). The most common intraoperative complication in each group was hemorrhage or vascular injury (table 3). One trocar related injury was reported (group ). In this patient a small mesenteric vessel was punctured during Veress needle placement, causing a selfcontained mesenteric hematoma. Minor bowel injury (colonic serosal injury) occurred in 1 patient in group, which was repaired with laparoscopic suturing without sequelae. Postoperative complications were similar in groups, and (19.9%, 21.5% and 26.5%, respectively). Notably more wound related complications and paralytic ileus were reported in the laparoscopic groups compared with the open group, perhaps due to differences in postoperative expectations and surgeon reporting (table 3). There were 2 postoperative deaths, each in group, namely inadvertent superior mesenteric artery transection followed by open revascularization and multi-organ failure in 1 patient and delayed candidemia with fungal myocarditis in 1. Table 4 lists pathological results. RCC was confirmed in 83%, 89% and 88% of the patients in groups, and, respectively. Pathological tumor stage was similar in groups and. There were 2 focally positive margins in group and none in the other groups. Adrenal pathology was similar among the groups. In group the outcomes of large tumors (greater than 7 to less than 10 cm) in 35 patients and very large tumors (10 cm or greater) in 30 were compared (table 5). Baseline demographics were similar in regard to patient age, gender and ASA score but median BMI was lower in patients with tumors greater than 10 cm (27 vs 33, p 0.04). Operative parameters (operative time, EBL and intraoperative complications) and perioperative parameters (hospital stay, morphine equivalents, postoperative complications and convalescence) were similar between the groups. Also, in group the 40 patients undergoing retroperitoneal radical nephrectomy were compared with the 25 undergoing transperitoneal radical nephrectomy (table 6). Tumor size was larger in the transperitoneal group (9 vs 10 cm, p 0.02). For all other perioperative and postoperative outcomes evaluated there was no difference between the retroperitoneal and transperitoneal approaches for T2 tumors. DISCUSSION With its oncological efficacy and superior recovery profile confirmed by numerous studies laparoscopic nephrectomy has emerged as the standard of care in most patients with T1 renal tumors who are not candidates for nephron sparing surgery. 2, 3, 7, 8 At our institution LRN has become a routine, efficacious and cost-effective surgical option in select patients 5, 11 with a renal mass. Clearly larger tumor size is a technical concern even in the hands of experienced laparoscopic surgeons. Initial reports of LRN involved relatively smaller renal tumors. Ono et al from Japan restricted their experience to tumors less than 5 cm and reported a mean tumor size of 3.1 cm in their 8-year experience. 3 Dunn et al reviewed the Washington University 9-year experience for LRN and stratified patients into small (4 cm or less) or large (greater than 4 cm) tumor. 8 All tumors were less than 10 cm. Although their cutoff between small and large tumors may be somewhat low, the study showed similar operative and postoperative outcomes between the groups. In the same study a comparison was performed between LRN and open radical nephrectomy for 4.1 to 10 cm tumors. Although operative time was longer in the laparoscopic group (5.9 vs 2.8 hours, p 0.001), EBL, analgesic use and hospital stay were significantly less. However, although time to normal activity was shorter (5.1 vs 7.6 weeks), the difference did not achieve statistical significance. With an upward shift in the tumor size cutoff in staging for T2 renal tumors from 4 to 7 cm in the TNM classification, 12 TABLE 1. Demographic data and preoperative tumor characteristics vs Demographics: Age (yrs) 67 0.001* 59 61 0.40 % ASA: 1 2 0.21 0 3 0.55 2 25 29 26 3 58 65 65 4 15 6 6 BMI 28 0.13 29 28 0.16 % Men/women 57.2/42.8 0.14 67.7/32.3 61.8/38.2 0.55 % Clinical status: Localized 95.7 0.15 90.8 88.2 0.69 Metastatic 4.3 9.2 11.8 Tumor characteristics: Median cm tumor size 4.5 (1.0 7.0) 0.001* 9.2 (7.1 16.0) 9.9 (7.3 14.0) 0.33 % Rt side 50.0 0.46 55.4 52.9 0.82 % Computerized tomography renal vein involvement 0.8 0.02 7.3 3.4 0.48 Significant (chi-square test p 0.05). vs

2174 LAPAROSCOPIC RADICAL NEPHRECTOMY FOR LARGE RENAL TUMORS TABLE 2. Intraoperative and postoperative data vs vs LAPT Intraop: Median operative time (mins) 180 (65 450) 0.08 180 (75 360) 207 (99 360) 0.03 Median EBL (ml) 100 (5 3,000) 0.001* 200 (50 1,800) 500 (100 3,500) 0.001 No. complications (%) 12 (7.2) 0.90 5 (7.7) 6 (17.6) 0.13 No. conversions to open (%) 2 (1.2) 0.37 Not applicable Not applicable Not applicable Median specimen wt (gm) 505 0.001* 889 719 0.09 Postop: Median mg morphine equivalents 17 (0 480) 0.99 24 (4 219) 400.0 (74 999) 0.001* Median days hospital stay 1.5 (1 14) 0.16 1.6 (1 13) 5.0 (4 11) 0.001* No. complications (%) 33 (19.9) 0.78 14 (21.5) 9 (26.5) 0.58 Median wks convalescence 4 (1 24) 0.88 4 (1 20) 8 (2 32) 0.02* TABLE 3. Complications No. (%) No. (%) No. (%) Intraop: Vascular/hemorrhage 8 (4.8) 4 (6.2) 6 (17.6) Bowel 1 (0.6) 1 (1.5) 0 Renal parenchymal 1 (0.6) 0 0 Spleen, liver 1 (0.6) 0 0 Other 1 (0.6) 0 0 Totals 12 (7.2) 5 (7.7) 6 (17.6) 0.90 0.13 Postop: Wound 10 (6.0) 3 (4.6) 1 (2.9) Delayed bleeding 6 (3.6) 3 (4.6) 4 (11.8) Pulmonary 5 (3.0) 1 (1.5) 2 (5.9) Ileus 4 (2.4) 3 (4.6) 0 Venous thromboembolism 1 (0.6) 0 1 (2.9) Acute renal failure 1 (0.6) 1 (1.5) 0 Cardiac 0 0 1 (2.9) Other 6 (3.6) 3 (4.6) 0 Totals 33 (19.8) 14 (21.4) 9 (26.4) 0.78 0.58 TABLE 4. Pathological findings vs vs No. pts 166 35 34 % Pathological findings: RCC 83.1 0.10 89.1 88.2 0.12 Other malignancy 0.0 1.6 8.8 Benign 16.9 9.4 2.9 % RCC tumor subtypes: Clear cell 75.2 0.20 78.6 89.7 0.56 Papillary 16.8 7.1 3.4 Chromophobe 5.1 10.7 6.9 % Pathological tumor stage: pt1 81.8 0.001* 0 0.0 0.74 pt2 3.6 57.9 50.0 pt3a 11.0 28.1 30.0 pt3b 3.6 12.3 20.0 pt3c 0.0 0.0 0.0 pt4 0.0 1.7 0.0 No. pos surgical margin 0 0.02* 2 0 0.30 % Adrenal pathology: None 32.5 0.96 35.4 44.1 0.69 Normal 65.1 61.3 52.9 RCC metastasis 1.2 1.5 2.9 Other benign findings 1.2 1.5 0.0 we reviewed our experience with LRN for tumors greater than 7 cm. The primary aim of the current study was to assess the safety and perioperative efficacy of LRN for larger (greater than 7 cm) renal tumors. Long-term oncological followup was not evaluated in this study. Our data demonstrate that compared with LRN for smaller T1 tumors (median size 4.5 cm) LRN for larger T2 tumors (median size 9.2 cm) results in similar rates of intraoperative complications (p 0.90), postoperative complications (p 0.78), conversion to open surgery (p 0.37), hospital stay (p 0.16) and convalescence (p 0.88). Although a somewhat larger extraction incision is necessary (6.5 vs 8.0 cm, p 0.0001), analgesic re-

LAPAROSCOPIC RADICAL NEPHRECTOMY FOR LARGE RENAL TUMORS 2175 TABLE 5. LRN for large (greater than 7 to less than 10 cm) vs very large (10 cm or greater) tumors Large Very Large No. pts 35 30 Pt demographics: Median tumor size (cm) 8.0 12.0 0.001* Median age 60 55 0.75 % Men/women 68/32 67/33 0.87 Median BMI 27 33 0.04* Median ASA score 3 3 0.94 Operative data: Median operative time (mins) 180 185 0.09 Median EBL (ml) 150 250 0.13 No. complications (%) 3 (8.6) 2 (6.7) 0.77 No. conversions to open (%) 0 0 Postoperative data: Median morphine equivalents 22.5 27.0 0.52 (mg) Median hospital stay (hrs) 38 48 0.08 No. complications (%) 8 (22.9) 6 (20.0) 0.78 Median convalescence (wks) 4 4 0.57 No. pos margin (%) 0 2 (6.9) 0.11 quirements are similar (p 0.99). Finally, although blood loss is statistically greater during LRN for T2 tumors (p 0.001), its clinical impact is negligible (100 vs 200 ml.). Stifelman et al performed a multi-institutional study of hand assisted laparoscopy for large renal specimens (greater than 7 cm). 13 When comparing perioperative outcomes, the only statistically significant difference was slightly shorter convalescence. However, this was of questionable clinical importance (18 vs 21 days, p 0.05). The complications, morbidity and mortality associated with open radical nephrectomy are available in a few published reports. 14 16 Nephrectomy performed via a midline incision for 193 tumors (mean tumor size 8.5 cm) was associated with a median blood loss of 935 ml, a 64% transfusion rate, and an intraoperative and postoperative complication rate of 20.7% and 19.1%, respectively. 14 More specifically splenic injury requiring splenectomy occurred in 24 patients (12.4%), significant vascular injury occurred in 16 (8.3%) and an incisional hernia developed in 4 (2.1%). The mortality rate was 2.1% and all patients who died postoperatively had metastatic disease. In another series of 656 radical nephrectomies performed between 1986 and 1997 via an anterior subcostal incision (mean tumor size 6.8 cm) the intraoperative and postoperative complication rates were 6.4% and 29.7%, respectively. 15 Specifically splenectomy due to iatrogenic injury was performed in 8% of patients and 32% received transfusion intraoperatively and/or postoperatively. The overall reoperation rate for managing complications was 2.3%. The mortality rate was 0.6%. Lastly, results from the National Veterans Administration Surgical Quality Improvement Program for 1,373 radical nephrectomies performed from 1991 to 1997 were reviewed. 16 The 30-day morbidity and mortality rates were 15% and 2%, respectively. Hemorrhage requiring the transfusion of more than 4 U packed red blood cells occurred in 1.9% of patients. These reported rates of morbidity are similar to those in our group. Notably a limitation of our study is the small number of patients in the group. From an oncological standpoint LRN for tumors greater than 7 cm appears to be efficacious. In our experience a 3.1% positive margin rate was noted, which was not statistically significant (p 0.30). Each patient with a positive surgical margin had a tumor greater than 10 cm, which was located anterior and apparently infiltrating the visceral peritoneum. Based on our experience with these 2 patients we now make a dedicated effort to excise an adequate patch of peritoneum en bloc with the tumor even during retroperitoneal nephrectomy. Stifelman et al reported a positive margin rate during hand assisted LRN similar to that for smaller tumors and only 1 recurrence (3%) in a 13.2-month followup. 13 Longer TABLE 6. Retroperitoneal vs transperitoneal approach in group Retroperitoneal Transperitoneal No. pts 40 25 Median pt demographics: Tumor size (cm) 9.0 10.0 0.02* Age 55 61 0.46 BMI 30 28 0.77 ASA score 3 3 0.44 Operative data: Median operative time 180 180 0.49 (mins) Median EBL (ml) 200 200 0.25 No. complications (%) 4 (10.0) 1 (4.0) 0.77 No. conversions to 0 0 open surgery (%) Postop data: Median specimen wt 860 1,002 0.38 (gm) No. pos margin (%) 2 (5) 0 0.26 No. complications (%) 7 (17.5) 7 (28.0) 0.78 follow data were reported by Portis et al, who documented 97% cancer specific survival and 92% recurrence-free survival at 5 years for tumors greater than 7 cm. 7 In our study perioperative outcomes were similar between LRN for large (greater than 7 to less than 10 cm) and very large (10 cm or greater) renal tumors. We report that LRN for larger T2 tumors can be performed transperitoneally or retroperitoneally. In our series the retroperitoneal approach was used in 61.5% of cases. While hilar control for T2 tumors is as equally rapid and efficacious as for smaller T1 tumors, subsequent mobilization of larger specimens is more challenging retroperitoneoscopically. In this regard, if necessary, intentional peritonotomy is created to provide adequate space to entrap the mobilized specimen. Early in our experience specimens were extracted through a flank incision by extending or connecting port sites. Currently most, if not all, specimens are extracted through a Gibson or Pfannenstiel incision and occasionally transvaginally in select females. We believe that this provides improved pain, recovery and cosmesis. Our current contraindications to LRN are tumors with vena caval thrombus, bulky lymphadenopathy or invasion of adjacent structures. Large size per se is only a relative contraindication, for which the experience of the individual laparoscopic surgeon is the primary determining factor. Larger renal tumors can have significant parasitic vessels that can increase the degree of intraoperative technical difficulty. On rare occasions preoperative angio-infarction of a large tumor may facilitate the performance of LRN. Certainly adequate laparoscopic experience is necessary before performing radical nephrectomy for large, stage T2 renal tumors. CONCLUSIONS LRN for larger renal tumors (greater than 7 cm) is feasible and efficacious. Surgical outcomes are comparable with those of LRN for smaller tumors (7 cm or less) and they offer the advantages of decreased blood loss, lesser complications and shorter hospital stay over open radical nephrectomy for select tumors greater than 7 cm. REFERENCES 1. Clayman, R. V., Kavoussi, L. R., Soper, N. J., Dierks, S. M., Meretyk, S., Darcy, M. D. et al: Laparoscopic nephrectomy: initial case report. J Urol, 146: 278, 1991 2. Chan, D. Y., Cadeddu, J. A., Jarrett, T. W., Marshall, F. F. and Kavoussi, L. 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