- Email: [email protected]
Cytoreductive laparoscopic radical nephrectomy
Urologic Oncology 6 (2001) 193–195
Original article
Cytoreductive laparoscopic radical nephrectomy: the early experience Stephen E. Pautler, M.D., W. Marston Linehan, M.D., McClellan M. Walther, M.D.* Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, USA Received 15 February 2001; accepted 13 March 2001
Abstract Laparoscopic radical nephrectomy is becoming increasingly utilized for localized renal tumors. We have applied this procedure to patients with metastatic disease for cytoreduction prior to systemic immunotherapy. Advantages of the laparoscopic approach include decreased parenteral narcotic requirement and decreased time to initiate systemic therapy. Herein, we describe the procedure with some technical pearls learned in our early experience. © 2001 Elsevier Science, Inc. All rights reserved. Keywords: Laparoscopy; Cytoreductive nephrectomy; Renal cancer; Immunotherapy
1. Introduction
2. Materials and methods
The indications for laparoscopic surgery have expanded in the field of urologic oncology. Since the introduction of laparoscopic nephrectomy by Clayman in 1991, multiple centers have evaluated this procedure with respect to cancer control, patient outcomes, and survival in patients with localized renal masses [1]. Overall, laparoscopic radical nephrectomy appears equivalent to open surgery with respect to cancer control and survival [2–4]. The recognized advantages of laparoscopy include decreased post-operative pain, faster recovery of normal activities, decreased length of hospital stay, and improved cosmesis [2–4]. We have expanded the indications of laparoscopic radical nephrectomy to include patients with bulky renal tumors and metastatic disease. At the National Cancer Institute, cytoreductive nephrectomy prior to systemic immunotherapy is employed as part of an ongoing phase III trial of highdose Interleukin-2 (IL-2) for patients with metastatic disease. In our experience, up to 40% with metastatic renal cancer may not be fit to receive high dose IL-2 after cytoreductive surgery [5]. With the noted advantages of laparoscopy, we previously evaluated the feasibility of laparoscopy in the cytoreductive setting and this article will review our experience.
Our approach to cytoreductive laparoscopic radical nephrectomy is a variant of the published technique described by Cadeddu [6]. Due to the large size of tumors in our series, a transperitoneal approach is used. Initially, the first port is placed using a Hassan technique, just lateral to the rectus, 2 finger-breaths below the umbilicus. After initial inspection of the abdomen for adhesions, metastases, and the renal mass, two further ports are placed. For right-sided tumors, a fourth port is placed in a sub-xiphoid location to facilitate liver retraction using a fan retractor.f1 Dissection commences with mobilization of the colon and small bowel to identify the renal hilum. On the right side, the vena cava is exposed and the upper pole is dissected to reveal the adrenal vein. After ligation of the right adrenal vein with clips, attention is turned to lower pole dissection and identification of the ureter. Following the ureter superiorly allows identification of the renal artery. We prefer to isolate the artery from the vein and ligate them separately. For the artery, three clips proximally are used. Careful inspection of the vein is required to ensure that it has collapsed and that no tumor thrombus exists. Laparoscopic ultrasound may be used if indicated. The renal vein is secured using an EndoGIA stapler (Ethicon Endo-Surgery Inc., Cincinnati, OH). Completion of the dissection includes incision of the lateral and superior attachments using a Harmonic Scalpel (Ethicon Endo-Surgery Inc., Cincinnati, OH). This instrument cuts tissue and controls vessels up to 3 mm in diameter. Specimens are removed either via a small
* Corresponding author. Bldg. 10, Rm. 2B47, 10 Center Drive, Bethesda, MD 10892, USA. Tel.: 1-301-402-2251; Fax: 1-301-496-0922. E-mail address: [email protected] (M.M.Walther).
1078-1439/01/$ – see front matter © 2001 Elsevier Science Inc. All rights reserved. PII: S1078-1439(01)00 1 3 8 - 7
194
S.E. Pautler et al. / Urologic Oncology 6 (2001) 193–195
lower midline incision or through a port following morcellation. Left-sided dissection is similar with identification of the renal vein as it passes over the aorta. Next, the left adrenal vein is identified at its confluence with the renal vein. After arterial ligation, the renal vein is stapled proximal to the adrenal and gonadal vein insertions. Further caudad, the gonadal vein is clipped and divided adjacent to the ureter. The remainder of the dissection is mirror image to the right side. Use of a hand-port for dissection or retraction may aid the completion of the procedure. Large tumors may be difficult to retract laterally during hilar dissection. For this reason, we do not release the lateral attachments of the kidney until the vessels have been secured. At times this may not be sufficient and hand retraction is necessary. Previously, Wolf et al. demonstrated decreased operative times using the handassisted approach to nephrectomy in a variety of conditions [7]. Unique problems encountered during cytoreductive nephrectomy include bulky tumor size, lymph node involvement, tumor thrombus, and local invasion (Fig. 1). Hilar lymphadenopathy may obscure the major vessels leading to inadvertent injury. With meticulous dissection and abundant use of clips, nodes may be reflected off of the vessels allowing completion of the procedure. Unrecognized tumor thrombus may be encountered during laparoscopic cytoreduction.
We, and other groups, have successfully completed the procedure if the thrombus involves the renal vein only. If the vena cava is involved, conversion to open is indicated. Local invasion by the renal primary may necessitate resection of the pancreatic tail, spleen, liver, or diaphragm. Adjunctive procedures must be assessed on a case-by-case basis. Use of the EndoGIA stapler facilitates pancreatic resection and ligation of the splenic hilum. Conversion to open surgery may be accomplished by connecting the two working ports to give fast and direct access to the renal hilum. Conversions to open may be required for slow progression of the dissection or to control hemorrhage from the hilum or parasitic tumor vessels. In our early experience with bulky tumors (median diameter 9 cm), conversion was required in about one-third of patients, more frequent than published rates for localized tumors [2–4]. 3. Comments Previously, we demonstrated the feasibility of laparoscopic cytoreductive nephrectomy [8]. In that study, three groups of patients undergoing cytoreduction were compared: (a) laparoscopic resection followed by specimen morcellation; (b) laparoscopic resection with removal through a small incision (laparoscopic-assisted nephrectomy); and (c) open nephrec-
Fig. 1. Computed tomography of a large left-sided tumor with hilar lymphadenopathy. This tumor was successfully resected laparoscopically.
S.E. Pautler et al. / Urologic Oncology 6 (2001) 193–195
tomy. Observed advantages in the morcellated group included decreased parenteral narcotic use and length of hospital stay. Also, time to treatment with systemic immunotherapy was shortest in this group. Median operative time was significantly increased for the laparoscopic approach with morcellation compared to open nephrectomy (466 min vs. 210 min, P0.001). The role of cytoreductive nephrectomy prior to immunotherapy remains undefined. The recently completed Southwest Oncology Group trial 8949, suggested a survival benefit of approximately 50% in patients undergoing open cytoreductive surgery followed by immunotherapy with interferon -2b [9]. This is the first randomized trial with statistically favorable outcomes in the surgery arm. A complete discussion of the issues surrounding this subject is beyond the scope of this article and we refer readers to a recent review by Yonover and Flanigan [10]. Three issues do merit discussion here. Firstly, patients were selected for surgery based on their ability to receive high-dose IL-2. These rigorous criteria have been previously published [11]. Patients with a caval thrombus, or tumors too large to fit in a morcellation sac (15-cm diameter) were not felt to be candidates for laparoscopic surgery. We did not endeavor to address the effect of laparoscopic cytoreductive nephrectomy on survival, but rather the feasibility of the technique. Secondly, contemporary surgical complication rates in series involving cytoreductive nephrectomy are 13% to 50% [5, 12–15]. In our pilot study, there was no difference in surgical complications between the laparoscopic and open surgical groups. Technical advantages of laparoscopy, such as decreased operative blood loss, were not realized in our early experience and may reflect the advanced nature of the disease. Despite this, the other advantages of decreased post-operative narcotic requirement and the shorter length of hospital stay suggest some benefit of laparoscopy. The last issue is the fact that a large proportion of patients undergoing cytoreductive nephrectomy does not receive immunotherapy. Despite similar inclusion criteria, different investigators have demonstrated that between 2% and 77% of patients do not complete the treatment plan, which is disconcerting [5,9, 12–15]. Protocol eligibility may vary from center to center based on treatment regimen. Patients not treated at NIH with high dose IL-2 are often referred to local physicians for low dose IL-2. Other causative factors for not receiving immunotherapy in these studies included rapid disease progression following surgery, post-operative complications, patient refusal, and incorrect pathology. It is our suspicion that laparoscopy may reduce the portion of our patients who do not receive immunotherapy, but this remains unproven. We were able to show a decrease in time from surgery to treatment with immunotherapy in our pilot study [8]. In the teaching setting, laparoscopic cytoreductive nephrectomy provides an excellent opportunity for learning complex ablative laparoscopic techniques. The learning curve with laparoscopic surgery is steep and contributes to the long
195
operative times [2,16,17]. The maneuvers required for laparoscopic cytoreductive nephrectomy are similar to those for localized disease and we believe, often more challenging. The training experience gained with large tumors, difficult hilar dissections, and major vessel dissection may allow urologists to become comfortable with laparoscopy. In our experience, laparoscopic cytoreduction is a technically feasible, yet challenging operation. Further experience with this procedure is required from other centers to validate our results.
References [1] Clayman RV, Kavoussi LR, Soper NJ, et al. Laparoscopic nephrectomy: initial case report. J Urol 1991;146:278–82. [2] Ono Y, Katoh N, Kinukawa T, Matsuura O, Ohshima S. Laparoscopic radical nephrectomy: the Nagoya experience. J Urol 1997;158: 719–23. [3] Barrett PH, Fentie DD, Taranger LA. Laparoscopic radical nephrectomy with morcellation for renal cell carcinoma: the Saskatoon experience. Urology 1998;52:23–8. [4] Dunn MD, Portis AJ, Shalhav AL, et al. Laparoscopic versus open radical nephrectomy: a 9-year experience. J Urol 2000;164:1153–9. [5] Walther MM, Alexander RB, Wiess GH, et al. Cytoreductive surgery prior to interleukin-2-based therapy in patients with metastatic renal cell carcinoma. Urology 1993;42:250–7. [6] Cadeddu JA. Laparoscopic Radical Nephrectomy. In: Bishoff JT and Kavoussi LR, editors. Atlas of Laparoscopic Retroperitoneal Surgery. Philadelphia: W. B. Saunders Company, 2000. pp. 83–104. [7] Wolf JS, Moon TD, Nakada SY. Hand assisted laparoscopic nephrectomy: comparison to standard laparoscopic nephrectomy. J Urol 1998;160:22–7. [8] Walther MM, Lyne JC, Libutti SK, Linehan WM. Laparoscopic cytoreductive nephrectomy as preparation for administration of systemic interleukin-2 in the treatment of metastatic renal cell carcinoma: a pilot study. Urology 1999;53:496–501. [9] Flanigan RC, Blumenstein BA, Salmon S, et al. Cytoreductive nephrectomy in metastatic renal cell cancer: the results of Southwest Oncology Group Trial 8949. J Urol 2000;163(Suppl):154. [10] Yonover PM, Flanigan RC. Should radical nephrectomy be performed in the face of surgically incurable disease? Curr Opin Urol 2000;10:429–34. [11] Robertson CN, Linehan WM, Pass HI, et al. Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells. J Urol 1990;144:614–8. [12] Rackley R, Novick A, Klein E, Bukowski R, McLain D, Goldfarb D. The impact of adjuvant nephrectomy on multimodality treatment of metastatic renal cell carcinoma. J Urol 1994;152:1399–403. [13] Bennett RT, Lerner SE, Taub HC, Dutcher JP, Fleischmann J. Cytoreductive surgery for stage IV renal cell carcinoma. J Urol 1995;154:32–4. [14] Franklin JR, Figlin R, Rauch J, Gitlitz B, Belldegrun A. Cytoreductive surgery in the management of metastatic renal cell carcinoma: the UCLA experience. Sem Urol Oncol 1996;14:230–6. [15] Levy DA, Swanson DA, Slaton JW, Ellerhorst J, Dinney CPN. Timely delivery of biological therapy after cytoreductive nephrectomy in carefully selected patients with metastatic renal cell carcinoma. J Urol 1998;159:1168–73. [16] Gill IS, Kavoussi LR, Clayman RV, et al. Complications of laparoscopic nephrectomy in 185 patients: a multi-institutional review. J Urol 1995;154:479–83. [17] Higashihara E, Baba S, Nakagawa K, et al. Learning curve and conversion to open surgery in cases of laparoscopic adrenalectomy and nephrectomy. J Urol 1998;159:650–3.
Original article
Cytoreductive laparoscopic radical nephrectomy: the early experience Stephen E. Pautler, M.D., W. Marston Linehan, M.D., McClellan M. Walther, M.D.* Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, USA Received 15 February 2001; accepted 13 March 2001
Abstract Laparoscopic radical nephrectomy is becoming increasingly utilized for localized renal tumors. We have applied this procedure to patients with metastatic disease for cytoreduction prior to systemic immunotherapy. Advantages of the laparoscopic approach include decreased parenteral narcotic requirement and decreased time to initiate systemic therapy. Herein, we describe the procedure with some technical pearls learned in our early experience. © 2001 Elsevier Science, Inc. All rights reserved. Keywords: Laparoscopy; Cytoreductive nephrectomy; Renal cancer; Immunotherapy
1. Introduction
2. Materials and methods
The indications for laparoscopic surgery have expanded in the field of urologic oncology. Since the introduction of laparoscopic nephrectomy by Clayman in 1991, multiple centers have evaluated this procedure with respect to cancer control, patient outcomes, and survival in patients with localized renal masses [1]. Overall, laparoscopic radical nephrectomy appears equivalent to open surgery with respect to cancer control and survival [2–4]. The recognized advantages of laparoscopy include decreased post-operative pain, faster recovery of normal activities, decreased length of hospital stay, and improved cosmesis [2–4]. We have expanded the indications of laparoscopic radical nephrectomy to include patients with bulky renal tumors and metastatic disease. At the National Cancer Institute, cytoreductive nephrectomy prior to systemic immunotherapy is employed as part of an ongoing phase III trial of highdose Interleukin-2 (IL-2) for patients with metastatic disease. In our experience, up to 40% with metastatic renal cancer may not be fit to receive high dose IL-2 after cytoreductive surgery [5]. With the noted advantages of laparoscopy, we previously evaluated the feasibility of laparoscopy in the cytoreductive setting and this article will review our experience.
Our approach to cytoreductive laparoscopic radical nephrectomy is a variant of the published technique described by Cadeddu [6]. Due to the large size of tumors in our series, a transperitoneal approach is used. Initially, the first port is placed using a Hassan technique, just lateral to the rectus, 2 finger-breaths below the umbilicus. After initial inspection of the abdomen for adhesions, metastases, and the renal mass, two further ports are placed. For right-sided tumors, a fourth port is placed in a sub-xiphoid location to facilitate liver retraction using a fan retractor.f1 Dissection commences with mobilization of the colon and small bowel to identify the renal hilum. On the right side, the vena cava is exposed and the upper pole is dissected to reveal the adrenal vein. After ligation of the right adrenal vein with clips, attention is turned to lower pole dissection and identification of the ureter. Following the ureter superiorly allows identification of the renal artery. We prefer to isolate the artery from the vein and ligate them separately. For the artery, three clips proximally are used. Careful inspection of the vein is required to ensure that it has collapsed and that no tumor thrombus exists. Laparoscopic ultrasound may be used if indicated. The renal vein is secured using an EndoGIA stapler (Ethicon Endo-Surgery Inc., Cincinnati, OH). Completion of the dissection includes incision of the lateral and superior attachments using a Harmonic Scalpel (Ethicon Endo-Surgery Inc., Cincinnati, OH). This instrument cuts tissue and controls vessels up to 3 mm in diameter. Specimens are removed either via a small
* Corresponding author. Bldg. 10, Rm. 2B47, 10 Center Drive, Bethesda, MD 10892, USA. Tel.: 1-301-402-2251; Fax: 1-301-496-0922. E-mail address: [email protected] (M.M.Walther).
1078-1439/01/$ – see front matter © 2001 Elsevier Science Inc. All rights reserved. PII: S1078-1439(01)00 1 3 8 - 7
194
S.E. Pautler et al. / Urologic Oncology 6 (2001) 193–195
lower midline incision or through a port following morcellation. Left-sided dissection is similar with identification of the renal vein as it passes over the aorta. Next, the left adrenal vein is identified at its confluence with the renal vein. After arterial ligation, the renal vein is stapled proximal to the adrenal and gonadal vein insertions. Further caudad, the gonadal vein is clipped and divided adjacent to the ureter. The remainder of the dissection is mirror image to the right side. Use of a hand-port for dissection or retraction may aid the completion of the procedure. Large tumors may be difficult to retract laterally during hilar dissection. For this reason, we do not release the lateral attachments of the kidney until the vessels have been secured. At times this may not be sufficient and hand retraction is necessary. Previously, Wolf et al. demonstrated decreased operative times using the handassisted approach to nephrectomy in a variety of conditions [7]. Unique problems encountered during cytoreductive nephrectomy include bulky tumor size, lymph node involvement, tumor thrombus, and local invasion (Fig. 1). Hilar lymphadenopathy may obscure the major vessels leading to inadvertent injury. With meticulous dissection and abundant use of clips, nodes may be reflected off of the vessels allowing completion of the procedure. Unrecognized tumor thrombus may be encountered during laparoscopic cytoreduction.
We, and other groups, have successfully completed the procedure if the thrombus involves the renal vein only. If the vena cava is involved, conversion to open is indicated. Local invasion by the renal primary may necessitate resection of the pancreatic tail, spleen, liver, or diaphragm. Adjunctive procedures must be assessed on a case-by-case basis. Use of the EndoGIA stapler facilitates pancreatic resection and ligation of the splenic hilum. Conversion to open surgery may be accomplished by connecting the two working ports to give fast and direct access to the renal hilum. Conversions to open may be required for slow progression of the dissection or to control hemorrhage from the hilum or parasitic tumor vessels. In our early experience with bulky tumors (median diameter 9 cm), conversion was required in about one-third of patients, more frequent than published rates for localized tumors [2–4]. 3. Comments Previously, we demonstrated the feasibility of laparoscopic cytoreductive nephrectomy [8]. In that study, three groups of patients undergoing cytoreduction were compared: (a) laparoscopic resection followed by specimen morcellation; (b) laparoscopic resection with removal through a small incision (laparoscopic-assisted nephrectomy); and (c) open nephrec-
Fig. 1. Computed tomography of a large left-sided tumor with hilar lymphadenopathy. This tumor was successfully resected laparoscopically.
S.E. Pautler et al. / Urologic Oncology 6 (2001) 193–195
tomy. Observed advantages in the morcellated group included decreased parenteral narcotic use and length of hospital stay. Also, time to treatment with systemic immunotherapy was shortest in this group. Median operative time was significantly increased for the laparoscopic approach with morcellation compared to open nephrectomy (466 min vs. 210 min, P0.001). The role of cytoreductive nephrectomy prior to immunotherapy remains undefined. The recently completed Southwest Oncology Group trial 8949, suggested a survival benefit of approximately 50% in patients undergoing open cytoreductive surgery followed by immunotherapy with interferon -2b [9]. This is the first randomized trial with statistically favorable outcomes in the surgery arm. A complete discussion of the issues surrounding this subject is beyond the scope of this article and we refer readers to a recent review by Yonover and Flanigan [10]. Three issues do merit discussion here. Firstly, patients were selected for surgery based on their ability to receive high-dose IL-2. These rigorous criteria have been previously published [11]. Patients with a caval thrombus, or tumors too large to fit in a morcellation sac (15-cm diameter) were not felt to be candidates for laparoscopic surgery. We did not endeavor to address the effect of laparoscopic cytoreductive nephrectomy on survival, but rather the feasibility of the technique. Secondly, contemporary surgical complication rates in series involving cytoreductive nephrectomy are 13% to 50% [5, 12–15]. In our pilot study, there was no difference in surgical complications between the laparoscopic and open surgical groups. Technical advantages of laparoscopy, such as decreased operative blood loss, were not realized in our early experience and may reflect the advanced nature of the disease. Despite this, the other advantages of decreased post-operative narcotic requirement and the shorter length of hospital stay suggest some benefit of laparoscopy. The last issue is the fact that a large proportion of patients undergoing cytoreductive nephrectomy does not receive immunotherapy. Despite similar inclusion criteria, different investigators have demonstrated that between 2% and 77% of patients do not complete the treatment plan, which is disconcerting [5,9, 12–15]. Protocol eligibility may vary from center to center based on treatment regimen. Patients not treated at NIH with high dose IL-2 are often referred to local physicians for low dose IL-2. Other causative factors for not receiving immunotherapy in these studies included rapid disease progression following surgery, post-operative complications, patient refusal, and incorrect pathology. It is our suspicion that laparoscopy may reduce the portion of our patients who do not receive immunotherapy, but this remains unproven. We were able to show a decrease in time from surgery to treatment with immunotherapy in our pilot study [8]. In the teaching setting, laparoscopic cytoreductive nephrectomy provides an excellent opportunity for learning complex ablative laparoscopic techniques. The learning curve with laparoscopic surgery is steep and contributes to the long
195
operative times [2,16,17]. The maneuvers required for laparoscopic cytoreductive nephrectomy are similar to those for localized disease and we believe, often more challenging. The training experience gained with large tumors, difficult hilar dissections, and major vessel dissection may allow urologists to become comfortable with laparoscopy. In our experience, laparoscopic cytoreduction is a technically feasible, yet challenging operation. Further experience with this procedure is required from other centers to validate our results.
References [1] Clayman RV, Kavoussi LR, Soper NJ, et al. Laparoscopic nephrectomy: initial case report. J Urol 1991;146:278–82. [2] Ono Y, Katoh N, Kinukawa T, Matsuura O, Ohshima S. Laparoscopic radical nephrectomy: the Nagoya experience. J Urol 1997;158: 719–23. [3] Barrett PH, Fentie DD, Taranger LA. Laparoscopic radical nephrectomy with morcellation for renal cell carcinoma: the Saskatoon experience. Urology 1998;52:23–8. [4] Dunn MD, Portis AJ, Shalhav AL, et al. Laparoscopic versus open radical nephrectomy: a 9-year experience. J Urol 2000;164:1153–9. [5] Walther MM, Alexander RB, Wiess GH, et al. Cytoreductive surgery prior to interleukin-2-based therapy in patients with metastatic renal cell carcinoma. Urology 1993;42:250–7. [6] Cadeddu JA. Laparoscopic Radical Nephrectomy. In: Bishoff JT and Kavoussi LR, editors. Atlas of Laparoscopic Retroperitoneal Surgery. Philadelphia: W. B. Saunders Company, 2000. pp. 83–104. [7] Wolf JS, Moon TD, Nakada SY. Hand assisted laparoscopic nephrectomy: comparison to standard laparoscopic nephrectomy. J Urol 1998;160:22–7. [8] Walther MM, Lyne JC, Libutti SK, Linehan WM. Laparoscopic cytoreductive nephrectomy as preparation for administration of systemic interleukin-2 in the treatment of metastatic renal cell carcinoma: a pilot study. Urology 1999;53:496–501. [9] Flanigan RC, Blumenstein BA, Salmon S, et al. Cytoreductive nephrectomy in metastatic renal cell cancer: the results of Southwest Oncology Group Trial 8949. J Urol 2000;163(Suppl):154. [10] Yonover PM, Flanigan RC. Should radical nephrectomy be performed in the face of surgically incurable disease? Curr Opin Urol 2000;10:429–34. [11] Robertson CN, Linehan WM, Pass HI, et al. Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells. J Urol 1990;144:614–8. [12] Rackley R, Novick A, Klein E, Bukowski R, McLain D, Goldfarb D. The impact of adjuvant nephrectomy on multimodality treatment of metastatic renal cell carcinoma. J Urol 1994;152:1399–403. [13] Bennett RT, Lerner SE, Taub HC, Dutcher JP, Fleischmann J. Cytoreductive surgery for stage IV renal cell carcinoma. J Urol 1995;154:32–4. [14] Franklin JR, Figlin R, Rauch J, Gitlitz B, Belldegrun A. Cytoreductive surgery in the management of metastatic renal cell carcinoma: the UCLA experience. Sem Urol Oncol 1996;14:230–6. [15] Levy DA, Swanson DA, Slaton JW, Ellerhorst J, Dinney CPN. Timely delivery of biological therapy after cytoreductive nephrectomy in carefully selected patients with metastatic renal cell carcinoma. J Urol 1998;159:1168–73. [16] Gill IS, Kavoussi LR, Clayman RV, et al. Complications of laparoscopic nephrectomy in 185 patients: a multi-institutional review. J Urol 1995;154:479–83. [17] Higashihara E, Baba S, Nakagawa K, et al. Learning curve and conversion to open surgery in cases of laparoscopic adrenalectomy and nephrectomy. J Urol 1998;159:650–3.