Laparoscopy and Robotics Elective Laparoscopic Partial Nephrectomy in Patients with Tumors >4 cm Soroush Rais-Bahrami, Frederico R. Romero, Guilherme C. Lima, Sahar Kohanim, Sompol Permpongkosol, Bruce J. Trock, Thomas W. Jarrett, and Louis R. Kavoussi OBJECTIVES METHODS
To assess the perioperative outcomes of elective laparoscopic partial nephrectomy to treat renal tumors in patients with tumor burdens ⬎4 cm compared with those with tumor burdens of ⱕ4 cm. A retrospective review of medical records was performed for all patients who had undergone laparoscopic partial nephrectomy for renal tumors from January 2000 to March 2005. The preoperative risk factors (ie, sex, age, American Society for Anesthesiologists score), perioperative course (ie, operative time, estimated blood loss, warm ischemia time, intraoperative and postoperative complications, transfusion rate, intraoperative biopsy of surgical margins, length of hospitalization), and pathologic outcomes (ie, tumor stage, type, and grade) were collected and compared between the patients in the 2 cohorts. Patients with larger tumors had significantly more complications (37.0% vs 21.8%, P ⫽ .039) and a significantly longer hospitalization (4.1 vs 3.0 days, P ⫽ .026). For those with malignant tumors ⬎4 cm compared with those with malignant tumors of ⱕ4 cm, the complication rate was 33.3% and 11.6% (P ⫽ 0.006) and the length of hospitalization was 4.5 and 3.2 days (P ⫽ .055), respectively. No other differences were noted between the 2 groups stratified by tumor size. Laparoscopic partial nephrectomy is an oncologically feasible option for tumor burdens ⬎4 cm in the greatest dimension to provide a nephron-sparing option for patients in whom individually selected lesions can be isolated. UROLOGY 72: 580 –583, 2008. © 2008 Elsevier Inc.
he safety and long-term oncologic efficacy have established open partial nephrectomy (OPN) as the preferred approach to treat most renal masses.1,2 The applications include elective management in individuals with a functional contralateral kidney.3 Laparoscopic partial nephrectomy (LPN) is a minimally invasive option initially applied to treat small peripheral tumors. This technique was developed to minimize the morbidity of established open nephron-sparing procedures long used for patients with compromised renal function. LPN has been used as treatment of larger tumors in patients with a solitary kidney or otherwise compromised renal function,4,5 and it continues to emerge as an attractive alternative to OPN because of its decreased morbidity and hospital costs, without compromising oncologic efficacy.6,7 The indications for LPN have expanded, and complex tumors are routinely approached using LPN at centers with technical expertise.8,9 When applied to larger tuFrom the Arthur Smith Institute for Urology, North Shore-Long Island Jewish Health System, Long Island, New York; James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland; and George Washington University Medical Center, Washington, DC Reprint requests: Louis R. Kavoussi, M.D., Arthur Smith Institute for Urology, North Shore University Hospital, 300 Community Drive, Tower 9, Manhasset, NY, 11030. E-mail: email@example.com Submitted: July 31, 2007, accepted (with revisions): May 15, 2008
© 2008 Elsevier Inc. All Rights Reserved
mors, LPN remains a technically demanding procedure, even for surgeons proficient in laparoscopy. The increasing tumor size presents unique challenges in extirpation and reconstruction.10 This study was undertaken to assess the perioperative and postoperative results of LPN in patients with tumor burdens ⬎4 cm compared with those with tumor burdens of ⱕ4 cm.
MATERIAL AND METHODS The records of 321 adult patients who had undergone LPN from January 2000 to March 2005 were retrospectively reviewed. The patients were divided into 2 cohorts: those with tumor burdens ⬎4 cm and those with tumor burdens ⱕ4 cm in greatest dimension. The overall surgical technique used was similar for all patients who underwent LPN during the study period, regardless of tumor size. In brief, after obtaining transperitoneal access to the kidney, laparoscopic ultrasonography was used to define the tumor extent. Depending on surgeon preference, the artery and vein were occluded or just isolated. When deemed necessary, vascular occlusion was accomplished with laparoscopic bulldog clamps or a laparoscopic Satinsky clamp without renal hypothermia (warm ischemia). The tumor was sharply excised, and multiple renal bed biopsies were obtained and sent for frozen section analysis. Diffuse parenchymal bleeding was controlled using a combination of argon beam coagulation and hemostatic tissue sealants. The collecting system was closed in select cases, and the renal parenchyma was reapproximated, as well as covered with fat. 0090-4295/08/$34.00 doi:10.1016/j.urology.2008.05.027
Table 1. Comparison of demographic, clinical, and outcome characteristics stratified by tumor size Tumor Size (cm) Variable Sex (n) Female Male Mean age ⫾ SD (y) Mean ASA score ⫾ SD Tumor side (n) Right Left Location (n) Lower Middle Upper Tumor status (n) Benign Malignant Mean tumor size ⫾ SD (cm) Stage (n) T1a or T1b T2 or T3 Grade (n) 1 2 3 4 Intraoperative complications (n) No Yes Postoperative complications (n) No Yes Transfusions (n) No Yes Mean operative time ⫾ SD (min) Mean clamp time ⫾ SD (min) Mean EBL ⫾ SD (mL) Mean LOH ⫾ SD (d) Intraoperative biopsy of surgical margins (n) Negative Positive
104 (38.0) 170 (62.0) 58.3 ⫾ 12.6 2.3 ⫾ 1
17 (50.0) 17 (50.0) 59.5 ⫾ 11.6 2.6 ⫾ 0.5
143 (52.2) 131 (47.8)
19 (55.9) 15 (44.1)
73 (40.6) 49 (27.2) 58 (32.2)
12 (54.6) 3 (13.6) 7 (31.8)
P Value .175 .592 .259 .684 .314
.501 87 (32.5) 181 (67.5) 2.3 ⫾ 0.87
13 (38.2) 21 (61.8) 5.8 ⫾ 1.52
243 (94.9) 13 (5.1)
23 (74.2) 8 (25.8)
13 (8.1) 112 (70.0) 34 (21.3) 1 (0.6)
1 (5.3) 11 (57.9) 7 (36.8) 0 (0.0)
261 (96.3) 10 (3.7)
24 (96.0) 1 (4.0)
212 (78.2) 59 (21.8)
17 (63.0) 10 (37.0)
187 (93.5) 13 (6.5) 183.6 ⫾ 63.3 23.0 ⫾ 12.6 322.1 ⫾ 233.3 3.0 ⫾ 1.3
22 (91.7) 2 (8.3) 199.2 ⫾ 57.2 21.9 ⫾ 13.7 406.3 ⫾ 354.3 4.1 ⫾ 2.7
155 (99.4) 1 (0.6)
18 (94.7) 1 (5.3)
⬍.0001 ⬍.0001 .482
.393 .039 .743 .168 .634 .124 .026 .206
ASA ⫽ American Society of Anesthesiologists; EBL ⫽ estimated blood loss; LOS ⫽ length of hospitalization. Data in parentheses are percentages.
The clinical parameters, including patient sex and age, American Society of Anesthesiologists score, operative time, estimated blood loss, warm ischemia time, transfusion rate, intraoperative and postoperative complications, intraoperative biopsy of surgical margins, length of hospitalization (LOH), tumor stage, and final pathologic features (tumor type and grade) were collected and compared between the 2 cohorts. The statistical analysis methods included 2 tests and t tests for comparing variables expressed as discrete categories or continuous variables, respectively. Statistical adjustment for potential confounding factors was performed with logistic regression analysis and analysis of variance or analysis of covariance. All statistical analyses were performed using Statistical Analysis Systems (SAS Institute, Cary, NC).
RESULTS Of the 321 patients reviewed, 274 (85.4%) had tumors ⱕ4 cm (range 0.8-4.0), 34 (10.6%) had tumors ⬎4 cm (range UROLOGY 72 (3), 2008
4.1-11), and 13 (4%) did not have tumor size data available. Of the 321 patients, 126 (39.3%) were women and 195 (60.7%) were men. Of the 321 patients, 205 (63.8%) had malignant tumors, 110 (34.3%) had benign, and 6 (1.9%) were without available notation of tumor malignancy status. No significant difference was found in the mean size between those with benign (mean 2.6 cm) and malignant (mean 2.7 cm) tumors (P ⫽ 0.386). Table 1 compares the demographic, clinical, and outcome characteristics between the 2 patient cohorts stratified by tumor size. Among the preoperative variables, only tumor stage differed significantly between the 2 groups, as expected, because the groups were defined by the tumor size.11 Patients with larger tumors had significantly more complications (Table 2) and a significantly longer LOH. When stratified by benign or malignant tumor type, only the patients with malignant tumors exhibited signifi581
Table 2. Incidence of intraoperative and postoperative complications stratified by tumor size
Tumor Size (cm) ⱕ4 ⬎4
Intraoperative Bleeding (⬎1000 mL) 3 (1.1) Splenic laceration 1 (0.4) Serosal tear of the bowel 2 (0.7) Ureteral injury 1 (0.4) Pleurotomy 1 (0.4) Lesion of renal hilum 1 (0.4) Persistent oozing from tumor 1 (4.0) bed Total 10 (3.7) 1 (4.0) Postoperative Urinary leakage 6 (2.2) 2 (7.4) Bleeding/anemia 5 (1.8) 3 (11.1) Atelectasis 18 (6.6) 2 (7.4) Pneumonia 2 (0.7) 3 (11.1) Urinary tract infection 1 (0.4) 1 (3.7) Urinary retention 7 (2.6) 1 (3.7) Acute renal failure 2 (0.7) 2 (7.4) Pleural effusion 2 (0.7) Orchalgia 2 (0.7) Postoperative pseudoaneurysm 1 (0.4) Thrombophlebitis 1 (0.4) Total 59 (21.8) 10 (37.0) Data presented as number of patients with percentages in parentheses.
cantly greater rates of complications or longer LOH, such as was associated with larger tumors. For those with benign tumors ⱕ4 cm vs those with tumors ⬎4 cm, the complication rate was 7.1% and 7.7%, respectively (P ⫽ 0.935), and the LOH was 2.7 and 3.3 days, respectively (P ⫽ 0.098). Among those with malignant tumors ⱕ4 cm vs those with tumors ⬎4 cm, the complication rate was 11.6% and 33.3%, respectively (P ⫽ 0.006), and the LOH was 3.2 and 4.5 days, respectively (P ⫽ 0.055). The complication rates were greater for patients aged ⱖ70 years (25.4%) compared with those ⬍70 years (7.4%; P ⫽ .0006). Older patients also tended to have a greater percentage of tumors ⬎4 cm (16.1% vs 9.8%), although this difference was not statistically significant (P ⫽ .152). Patients with tumors ⬎4 cm had more than twice the odds of complications (odds ratio 2.8, 95% confidence interval 1.2-6.8; P ⫽ .023). Adjustment for age did not appreciably alter the effect of the tumor size. When patients were stratified by benign vs malignant status, the effect of tumor size among patients with malignant tumors became somewhat stronger (odds ratio 3.2, 95% confidence interval 1.1-9.2); this estimate was adjusted for the effect of age because some confounding was evident. No other differences were apparent between the groups as defined by tumor size. The associations with surgical outcomes were not altered by adjustments for age, tumor location, or American Society of Anesthesiologists score. 582
COMMENT Partial nephrectomy was initially applied to treat patients with bilateral renal tumors or those with unilateral renal tumors with an absent or poorly functioning contralateral kidney. Over time, the indications for partial nephrectomy were broadened to include selected patients with a normal contralateral kidney,12 including those with peripheral tumors ⱕ4 cm in size (Stage T1a according to the 2002 TNM classification of renal cell carcinoma). The efficacy of partial nephrectomy in patients with small tumors ⬍4 cm is now widely accepted. Such evidentiary success has recently made this procedure the standard for the treatment of small renal tumors. The perception that larger T1 tumors, 4-7 cm (Stage T1b), have a poorer prognosis has established 4 cm as the cutoff size for the treatment of renal neoplasms using partial nephrectomy. In 2004, several studies have shown results supporting a different concept, specifically demonstrating that lesions 4-7 cm have a worse prognosis, regardless of treatment modality, whether radical or partial nephrectomy.13,14 They demonstrated that radical nephrectomy has no advantages compared with partial nephrectomy in terms of cancer-specific survival or recurrence rates for tumors as large as 7 cm. These results might suggest that the size criteria for indicated partial nephrectomy can be expanded to include both T1a and T1b renal neoplasms. LPN continues to emerge as a safe and efficacious procedure in the management of renal tumors, fully duplicating the open technique. In selected centers, the laparoscopic surgical modality is considered the standard treatment of small renal tumors. Accordingly, consideration to expand the surgical indications for LPN to also include renal lesions ⬎4 cm, such as has been done for OPN, is tempting. With increasing experience, it has become evident that larger tumors can also be approached laparoscopically while reproducing the OPN technique with adequate resection of lesions exceeding the well-accepted 4-cm cutoff.5 Extensive renal parenchyma resection intuitively would appear to have a greater risk of complications. Transection of major intrarenal blood vessels and calices of the collecting system can result in a greater risk of hemorrhage and urinary leakage. Furthermore, the extended parenchymal resection could result in a lower postoperative glomerular filtration rate. In our series, patients with tumors ⬎4 cm had a greater incidence of postoperative complications than did the patients with Stage T1a tumors. These patients experienced bleeding (11.1% vs 1.8%), urinary leakage (7.4% vs 2.2%), and acute renal failure (7.4% vs 0.7%) complications more often. As a result, they required a longer LOH. These differences were greater in patients with malignant tumors, presumably because of the pronounced neovascularity and bleeding associated with renal cell carcinoma. The greater incidence of infectious complications— UROLOGY 72 (3), 2008
pneumonia and urinary tract infection—found in these patients might have been a consequence of the extended hospitalization. This retrospective study had the limitations and biases of all nonprospective, nonrandomized, single-center series, including potential selection bias, surgeon bias, incomplete information, and a relatively small sample size. Despite these limitations, and even though the incidence of postoperative complications was greater in our series, LPN in patients with selected T1b and T2 renal tumors might be advantageous. Most of these complications were usually mild and transitory, and patients might benefit after the remaining nephrons recover. Additionally, this experience was an initial experience, and, with time, the complication rates are expected to decrease.
CONCLUSIONS Our initial experience of LPN for tumors ⬎4 cm was associated with a significantly greater rate of complications and longer postoperative hospital stay. These differences were primarily associated with malignant tumors. Although patients aged ⱖ70 years had significantly greater complication rates and a nonsignificantly greater fraction of tumors measuring ⬎4 cm, the association between tumor size and complication rates was not a statistical artifact confounded by age alone. Nevertheless, the postoperative oncologic efficacy of the procedure, as determined by surgical margins, was not significantly different when comparing patients divided by tumor size. A long-term follow-up study is needed to fully realize the possible benefits of providing elective LPN to patients with larger tumor burdens.
UROLOGY 72 (3), 2008
References 1. Gill IS, Kavoussi LR, Lane BR, et al. Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol. 2007;178:41-46. 2. Breda A, Stepanian SV, Liao J, et al. Positive margins in laparoscopic partial nephrectomy in 855 cases: A multi-institutional survey from the United States and Europe. J Urol. 2007;178:47-50. 3. Uzzo RG, Novick AC. Nephron sparing surgery for renal tumors: Indications, techniques, and outcomes. J Urol. 2001;166:6-18. 4. Gill IS, Colombo JR, Moinzadeh A, et al. Laparoscopic partial nephrectomy in solitary kidney. J Urol. 2006;175:454-458. 5. Gill IS, Desai MM, Kaouk JH, et al. Laparoscopic partial nephrectomy for renal tumor: Duplicating open surgical techniques. J Urol. 2002;167:469-476. 6. Beasley KA, Al Omar M, Shaikh A, et al. Laparoscopic versus open partial nephrectomy. Urology. 2004;64:458-461. 7. Allaf ME, Bhayani SB, Rogers C, et al. Laparoscopic partial nephrectomy: Evaluation of long-term oncological outcome. J Urol. 2004;172:871-873. 8. Finelli A, Gill IS. Laparoscopic partial nephrectomy: Contemporary technique and results. Urol Oncol. 2004;22:139-144. 9. Frank I, Colombo JR, Rubinstein M, et al. Laparoscopic partial nephrectomy for centrally located renal tumors. J Urol. 2006;175: 849-852. 10. Kim FJ, Rha KH, Hernandez F, et al. Laparoscopic radical versus partial nephrectomy: Assessment of complications. J Urol. 2003; 170:408-411. 11. Fleming ID, for the American Joint Committee on Cancer. AJCC Cancer Staging Manual, 5th ed. Philadelphia: Lippincott-Raven; 1997. 12. Joniau S, Vander Eeckt K, Van Poppel H. The indications for partial nephrectomy in the treatment of renal cell carcinoma. Nat Clin Pract Urol. 2006;3:198-205. 13. Patard JJ, Shvarts O, Lam JS, et al. Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience. J Urol. 2004;171:2181-2185. 14. Leibovich BC, Blute ML, Cheville JC, et al. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. J Urol. 2004;171:1066-1070.
To assess the perioperative outcomes of elective laparoscopic partial nephrectomy to treat renal tumors in patients with tumor burdens > 4 c...
Published on Sep 1, 2008
To assess the perioperative outcomes of elective laparoscopic partial nephrectomy to treat renal tumors in patients with tumor burdens > 4 c...