Curr Urol Rep (2014) 15:377 DOI 10.1007/s11934-013-0377-y
KIDNEY DISEASES (G CIANCIO, SECTION EDITOR)
Perioperative Complications of Robot-Assisted Partial Nephrectomy Eric H. Kim & Jeffrey A. Larson & Michael Figenshau & R. Sherburne Figenshau
Published online: 17 December 2013 # Springer Science+Business Media New York 2013
Abstract The incidence of renal cell carcinoma continues to increase with utilization of diagnostic abdominal imaging with migration towards a proportionally greater detection of small renal masses (SRM). Robot-assisted partial nephrectomy (RAPN) has become an attractive minimally invasive treatment modality for SRM’s due to the technical advantages and shortened learning curve compared to laparoscopic partial nephrectomy (LPN) while preserving comparable perioperative outcomes. With advances in ablative approaches for stage I renal cell carcinoma (RCC) and controversy surrounding the role of extirpative surgery for SRM’s, systematic understanding of the complications associated with RAPN has become even more imperative. This review aims to summarize and evaluate the contemporary literature, compile reported intraoperative complications, describe conventional and nephronsparing surgery (NSS) specific postoperative complications, and assess factors associated with an increased likelihood for perioperative complications following RAPN. Keywords Robot-assisted partial nephrectomy . RAPN . Robotic partial nephrectomy . Partial nephrectomy . Nephrectomy . Nephron-sparing surgery . NSS . Partial nephrectomy complication . Laparoscopic partial nephrectomy complication . Minimally-invasive complication . Da Vinci This article is part of the Topical Collection on Kidney Diseases E. H. Kim : J. A. Larson : M. Figenshau : R. S. Figenshau (*) Division of Urologic Surgery, Washington University School of Medicine, 4960 Children’s Place, Campus Box 8242, Saint Louis, MO 63110, USA e-mail: [email protected]
Introduction Due to the increased utilization of diagnostic abdominal imaging in recent years, the incidence of renal cell carcinoma (RCC) continues to increase. The American Cancer Society predicts 65,150 new RCC cases and 13,680 RCC deaths in the United States in 2013 [1]. There has also been proportionally greater detection of stage I disease and migration towards smaller tumor size within this stage [2]. In light of evidence that nephron-sparing surgery (NSS) provides favorable oncologic outcomes [3] and that radical nephrectomy (RN) is associated with significant morbidity and mortality [4], the American Urological Association (AUA) guidelines currently recommend partial nephrectomy (PN) as the standard of care for T1a tumors and as an alternative treatment for T1b tumors [5]. Robot-assisted partial nephrectomy (RAPN) has become a wide spread NSS modality because of the shortened learning curve compared to laparoscopic partial nephrectomy (LPN) [6] while achieving comparable perioperative outcomes [7]. With advances in ablative approaches for stage I RCC and recent controversy surrounding the role of extirpative surgery for small renal masses, systematic understanding of the complications associated with RAPN has become even more imperative. This review aims to summarize and evaluate the contemporary literature; compile reported intraoperative complications; describe conventional and NSS-specific postoperative complications; and assess factors associated with an increased likelihood for perioperative complications following RAPN.
E. H. Kim e-mail: [email protected]
Contemporary Series
J. A. Larson e-mail: [email protected]
As experience with RAPN has grown, studies successively updating single and multi-institutional perioperative complication rates of RAPN have been published. Table 1 summarizes contemporary studies with greater than 100 RAPN cases
M. Figenshau e-mail: [email protected]
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and their associated perioperative complication rates. In studies where complications were not categorized by ClavienDindo grade [8], we have attempted to do so based on the information provided. Although some more recent studies likely incorporate data from previously published reports, eliminating this redundancy was not feasible or substantively illustrative. Overall, RAPN is safe with reported intraoperative complication rates ranging from 1.4 % to 2.9 %, Clavien grade 1-2 postoperative complication rates ranging from 3.1 to 22.5 %, and Clavien grade 3-4 postoperative complication rates ranging from 2.0 % to 10.4 % [9••, 10–16]. Only one perioperative mortality occurred among all of the published studies [15]. Tanagho et al., have published the largest series to date with 886 patients included in their analysis. They report an intraoperative complication rate of 2.6 %, conversion rate of 0.8 %, and major (Clavien >3) postoperative complication rate of 3.6 % [9••]. This study is representative of the collection of contemporary series in Table 1. Generally, intraoperative complications are few, with intraoperative conversion to RN or to non-robotic PN even fewer. Additionally, minor postoperative complications (Clavien 1 and 2) were more common than major postoperative complications (Clavien 3 and 4). Death (Clavien 5 complication) in the postoperative period following RAPN was exceedingly rare. Conversion to other PN techniques and conversion to RN were not considered to be intraoperative complications by some authors. Spana et al., reported eight intraoperative complications, although they also reported six conversions to robotic RN that were not included as complications [12]. Scoll et al., and Rogers et al., report conversion rates to non-robotic PN modalities without specific mention of intraoperative complication rates [15, 16]. The seemingly broad range among postoperative complication rates are likely a result of under-reporting on the part of some studies. In studies where postoperative complications were not specifically categorized by Clavien grade, minor and clinically insignificant complications were likely omitted. This is evidenced by the reported Clavien grade 1-2 complication rates ranging from 3.1 to 22.5 %, depending on the study. Additionally, standardized definitions across all studies did not exist for all minor complications.
Intraoperative Complications Intraoperative complications of RAPN include vascular and visceral injury from laparoscopic access as well as hemorrhage and injury to adjacent structures, which may require conversion to laparoscopic, open, or radical nephrectomy. Access to the peritoneal cavity or retroperitoneal space with insufflation is necessary to achieve a working area for robotic surgery. Several techniques used to achieve
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laparoscopic access include classic pneumoperitoneum (Veress needle), open (Hasson) entry, direct trocar insertion, radially expanding trocars, and visual entry systems. Minor complications associated with access include extraperitoneal insufflation and skin or subcutaneous bleeding. Major complications include vascular or gastrointestinal injury as well as bladder, ureteral or solid organ perforation. A meta-analysis of laparoscopic entry techniques found vascular injuries to occur in 0.1 % and bowel injuries in 0.18 % of cases [17•]. Many retrospective and randomized controlled trials have attempted to identify the safest method of laparoscopic access. The updated meta-analysis of 28 randomized control trials with 4860 patients evaluating the various methods of access showed no advantage of any technique in preventing major complications [17•]. Using an open entry technique did reduce the incidence of failed entry, extraperitoneal insufflation, and omental injury but did not demonstrate lower vascular or visceral injury rates. Although RAPN is safe, the largest studies (Table 1) reported an intraoperative hemorrhage in 18 patients out of 2118 cases (0.8 %). The described causes are renal veinotomy, injury to the inferior vena cava (IVC), trocar injury to the inferior mensenteric artery (IMA), splenic laceration and renal hemorrhage from an unidentified unclamped renal artery. Likewise, injury to adjacent structures including bowel, spleen, liver, and pancreas was reported in five patients (0.2 %). Conversion to traditional laparoscopic partial nephrectomy (PN) or radical nephrectomy (RN )is also a rare event, reported in only 19 patients (0.8 %). Conversions were required for a wide variety of reasons including positive surgical margins, satellite lesions, perinephric scarring, indeterminate ultrasound tumor localization, and an endophytic tumor not amenable to NSS.
Postoperative Complications Conventional Many of the postoperative complications following RAPN are not unique to kidney surgery or use of robotic techniques. These conventional postoperative complications can be separated broadly into potentially life threatening and non-life threatening. The common non-life threatening complications following RAPN include gastrointestinal, pulmonary, and wound-related complications. Tanagho et al., Spana et al., and Rogers et al. ,have reported similar rates of ileus after RAPN: 1.2 % (11/886), 1.1 % (5/450), and 2.0 % (3/148), respectively [9••, 12, 16]. Many other contemporary studies, however, do not list ileus as a postoperative complication. The significantly decreased rate of ileus following laparoscopic
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Table 1 Summary of RAPN perioperative complications by study Study
Number of patients
Years enrolled
Intraop. complication rate
Conversion to PN (non-RAPN)
Conversion to RN
Postop. complication rate Clavien 1-2
Clavien 3-4
Clavien 5
Tanagho et al., 2013 [9••]
886
2007-2011
2.6 %
0.3 %
0.5 %
12.1 %
3.6 %
0%
Mathieu et al., 2013 [10] Ficarra et al., 2012 [11] Spana et al., 2011 [12] Kaouk et al., 2011 [13] Benway et al., 2010 [14] Scoll et al., 2010 [15] Rogers et al., 2008 [16]
240 347 450 252 183 100 148
2009-2011 2008-2010 2006-2009 2007-2010 2006-2008 2007-2009 2002-2007
n/a 2.9 1.8 2.0 2.7 n/a n/a
n/a 0% 0.7 % 2.0 % 1.1 % 1.0 % 1.4 %
n/a 0.6 % 1.6 % 0% 0% 1.0 % 0%
22.5 % 8.9 % 12.0 % 16.7 % 3.8 % 7.0 % 6.8 %
10.4 % 2.9 % 3.8 % 2.4 % 3.3 % 5.0 % 2.0 %
0% 0% 0% 0% 0% 1.0 % 0%
% % % %
intraop. = intraoperative, PN = partial nephrectomy, RN = radical nephrectomy, postop. = postoperative
approaches to nephrectomy, likely a result of decreased narcotic pain medication requirement and early ambulation, have been previously reported [18]. The same benefit is likely afforded to robotic approaches to nephrectomy. Non-life threatening pulmonary complications following RAPN, including dyspnea, atelectasis, pulmonary edema, and pneumonia, occurred at similar rates to ileus. Tanagho et al., Spana et al., and Kaouk et al., report these pulmonary complication rates as 1.4 % (12/886), 1.3 % (6/450), and 0.4 % (1/252), respectively [9••, 12, 13]. Wound-related complications, including local infection and hernia, occurred even less frequently. Tanagho et al., Spana et al., Kaouk et al., and Benway et al., report wound-related complication rates of 0.8 % (7/886), 0.7 % (3/450), 0.8 % (2/252), and 0.5 % (1/ 183), respectively [9••, 12–14]. Overall, the conventional nonlife threatening postoperative complications common to most abdominal surgeries occur at a relatively low frequency following RAPN. Thrombosis and cardiovascular events comprise the majority of potentially life-threatening postoperative complications common to abdominal surgery. Although urologic patients are typically of advanced age, cardiovascular postoperative complications following urologic surgery are relatively few compared to other surgical series [19]. Furthermore, cardiovascular events including arrhythmia and myocardial infarction (MI) are rare following RAPN. Tanagho et al., reports MI in 0.1 % (1/886) and arrhythmia in 0.5 % (4/886) of patients [9••]. Ficarra et al., reports MI in 0.3 % (1/347) and arrhythmia in 1.2 % (4/347) of patients [11]. Multiple studies including those by Spana et al., Kaouk et al., and Mathieu et al., report no occurrences of postoperative MI. Only one fatal postoperative MI is reported among the contemporary studies, occurring in the operating room during port site closure [15]. Likely the low cardiovascular complication rate of RAPN reflects the largely elective nature of the surgery, as the majority of tumors treated with RAPN are low stage [13–16].
The risk of thrombosis and thromboembolic complications following laparoscopic surgery has been well documented [20]. Although prevention strategies have diminished the incidence of postoperative thrombosis after urologic laparoscopic surgery [21], the risk of thromboembolic complications after RAPN is not negligible. For instance, pulmonary embolism was reported in 0.6 % (5/886), 1.6 % (7/450), 1.2 % (3/ 252), 2.0 % (2/100), and 1.4 % (2/148) of patients in contemporary series [9••, 12, 13, 15, 16]. Specific to Nephron-Sparing Surgery Although RAPN provides some technical benefits over LPN, the NSS-specific postoperative complications are common to both modalities [7, 22]. Specifically, these include bleeding complications requiring transfusion and/or additional procedures, urinary leakage as a result of collecting system violation, renal injury possibly related to warm ischemia time, and rarely, port-site metastases. Some of these NSS-specific complications are summarized in Table 2. Bleeding represents the most common postoperative complication following RAPN [9••, 10–16]. Postoperative bleeding complications following RAPN, including hematoma, hemorrhage, and pseudoaneurysm, ranged from 0.7 % to 12.3 % dependent on study [9••, 10–16]. Detection of postoperative hemorrhage is often driven by clinical presentation and confirmed by serial laboratory monitoring. As the larger series included in Table 2 show, postoperative bleeding requiring transfusion occurred in roughly 4 % of cases (4.2 % Tanagho et al., 3.7 % Ficarra et al., 4.2 % Spana et al.) [9••, 11, 12]. Postoperative transfusion rates following LPN are similar, with large studies reporting rates of 2.7 % and 4.5 % [23, 24]. Postoperative transfusion rate was substantially higher in the series reported by Kaouk et al., at 11.5 % [13]. Presumably, this represents a difference in transfusion criteria by institution rather than a difference in clinically significant bleeding.
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Table 2 Summary of NSS-specific postoperative complications following RAPN by study Study
Number of patients
Bleeding
Requiring transfusion
Pseudoaneurysm
Urine leak
Renal failure
Requiring hemodialysis
Tanagho et al., 2013 [9••] Mathieu et al., 2013 [10] Ficarra et al., 2012 [11] Spana et al., 2011 [12]
886 240 347 450
5.8 8.3 5.2 5.6
4.2 % n/a 3.7 % 4.2 %
1.1 3.8 1.4 0.2
%* % %* %
1.1 1.3 0.6 1.6
% % % %
0.7 % n/a 0% 0.2 %
0.2 % n/a 0% n/a
Kaouk et al., 2011 [13] Benway et al., 2010 [14] Scoll et al., 2010 [15] Rogers et al., 2008 [16]
252 183 100 148
12.3 % 3.8 % 3.0 % 0.7 %
11.5 % 1.1 % 3.0 % 0%
0.8 %* 1.6 % 1.0 % 0%
1.6 1.1 2.0 1.4
% % % %
0.8 % 0% 0% 0%
0.4 % 0% 0% 0%
% % % %
*bleeding requiring angioembolization was used as a surrogate for pseudoaneurysm
Although renal pseudoaneurysm following PN is traditionally considered a rare complication [25], it is more strongly associated with minimally invasive PN [26]. Reported rates of pseudoaneurysm following RAPN ranged from 0.2 % to 3.8 % depending on the study [9••, 10–16]. Although pseudoaneurysm was not specifically mentioned by Tanagho et al., Ficarra et al., and Kaouk et al., delayed hemorrhage requiring angioembolization was considered a surrogate. Typically, renal pseudoaneurysm presents as delayed gross hematuria and is associated with the treatment of centralized tumors [26, 27]. The gold standard for diagnosis and treatment of renal pseudoaneurysm remains selective angiography and embolization. Postoperative urinary leakage occurs as a result of collecting system violation during tumor excision and is specific to PN. Clinically, urine leak following RAPN may present as ileus, abdominal distention, electrolyte derangement, or increased surgical drain output. When no percutaneous drain was placed intraoperatively, management requires procedural intervention, such as ureteral stent, percutaneous drain, or percutaneous nephrostomy. Reported rates of urine leak following RAPN ranged from 0.6 % to 2.0 % depending on study [9••, 10–16], which was similar to reported urine leak rates following LPN in two large studies (1.9 % and 2.0 %) [23, 24]. Extrapolating from LPN studies, urine leak after RAPN is likely more common following resection of larger and deeper tumors [28, 29]. All of the reported urine leakage complications were successfully managed with percutaneous or ureteral drainage and did not require renal re-operation [9••, 10–16]. Reported rates of postoperative renal insufficiency were overall low, ranging from 0 % to 0.8 % depending on the study [9••, 11–16]. Although standardized definitions of postoperative renal insufficiency based on objective measures such as change in urine output or serum creatinine were not given, clinically significant postoperative renal insufficiency requiring hemodialysis was correspondingly low, ranging from 0 % to 0.4 % depending on the study [9••, 11, 13–16].
The decreased incidence of renal failure following RAPN may be a result of diminished warm ischemia time (WIT) as compared to LPN [7]. Higher WIT has been associated with renal functional deterioration following PN in the short and long term [30]. However, given that functional outcomes after PN are also strongly correlated to non-modifiable factors such as amount of renal parenchyma excised and baseline renal function [31, 32], the decreased incidence of renal failure following RAPN may represent patient selection. Port-site metastasis (PSM) is an exceedingly rare complication of laparoscopic oncologic surgery. The most recent review of the literature on renal cell carcinoma PSM reports nine previous cases following laparoscopic RN or PN and the first instance of renal cell carcinoma PSM following RAPN. Confirming previous reviews, the review states that contributing factors to PSM occurrence include patient immunosuppression, biologic aggressiveness of the tumor, and techniquerelated factors such as specimen morcellation and failure to use an entrapment bag [33].
Factors Predictive of Complications As expected with any surgical approach, perioperative outcomes improve with increased surgeon experience. Mottrie et al., demonstrated that progression of the surgeon learning curve was associated with decreased WIT, total operative time, and estimated blood loss (EBL) [34]. The improvement in perioperative measures with increased experience translates to decreased perioperative complication rate, as surgeons new to RAPN are likely to experience twofold to threefold higher complication rates. Mathieu et al. and Ficarra et al. demonstrated that the hazard ratio for perioperative complications was 2.14 and 2.99 for the first 20 and 30 cases in a surgeon's experience, respectively [10, 11]. Although increasing surgeon experience diminishes the risk, non-modifiable baseline patient characteristics also contribute to the likelihood of perioperative complications. Often
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advanced age is used as a surrogate for baseline comorbidity and is assumed to correlate with complication risk. However, Hillyer et al., demonstrated in a matched cohort study that age greater than 70 years does not correlate with an increased risk of perioperative complications [35]. Patient body-mass index (BMI) provides a rough measure of baseline comorbidity and increases the technical difficulty of RAPN and may predispose the patient to more complications [36]. However, multiple studies have demonstrated no significant association between perioperative complications and BMI for patients undergoing RAPN. Naeem et al., demonstrated no significant difference in complications between patients based on BMI less than or greater than 30 kg/m2 [37]. Kiziloz et al., and Isac et al., found no significant difference in complications when patients were further sub-stratified into categories based on ranges of BMI [38, 39]. However, all three studies demonstrated a significant association between higher BMI and increased EBL [37–39]. Gorin et al., may have clarified the distinction by demonstrating that BMI and outer abdominal fat are not associated with increased complication rate, whereas increasing intraabdominal fat is significantly associated with complications [40]. Recently developed grading systems for renal tumors considered for PN include the RENAL nephrometry score [41] and PADUA classification [42]. Both grading systems have been validated as independent predictors of complications following PN, with four times greater odds of complication when the RENAL score is 9 or greater and when the PADUA classification is 10 or greater [43]. Specific to RAPN, increasing RENAL score appears to be associated with higher overall complication rates and major complication rates. Tanagho et al., found that in patients undergoing RAPN, RENAL scores of 4-6, 7-9, and 10-12 resulted in complication rates of 11, 18, and 23 %, respectively [9]. Simhan et al., found that, in patients undergoing PN, of which roughly half underwent RAPN, RENAL scores of 4-6, 7-9, and 10-12 resulted in major complication rates of 6, 11, and 22 %, respectively [44]. Nevertheless, the RENAL score may not be a strong predictor of complications following RAPN, as the correlation found by Tanagho et al., was small (OR=1.18) and other studies have found no significant association between RENAL score and RAPN perioperative complications [9••]. Similarly, PADUA classification has been found to be a significant but weak predictor of complications following RAPN (OR=1.04) [11]. The decreased strength of correlation between anatomic renal tumor grading systems and complications for patients undergoing RAPN as compared to LPN or OPN may be a result of increased surgeon experience as well as a technical advantage of robotic approaches to PN. Additionally, individual components of the RENAL score and PADUA classification have been examined for association with complication rates. Patel et al., demonstrated that the
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distinction between tumors equal to or less than 4 cm (stage T1a) and tumors greater than 4 cm did not predict occurrence of a perioperative complication after RAPN [45]. Both Tanagho et al., and Ficarra et al., demonstrated that tumor size, when evaluated as a continuous variable, has a small but statistically significant correlation to perioperative complications after RAPN [9••, 11]. Although the increased difficulty of renal dissection in the case of hilar tumors seems apparent, Dulabon et al., found that hilar tumor location was not significantly associated with complications after RAPN [46]. Other studies have demonstrated that tumor proximity to the collecting system is the characteristic most strongly correlated to complication rates, likely as a result of increased collecting system violation and associated sequela. Mathieu et al., found that collecting system violation had a threefold higher association with major complications [10]. While evaluating the RENAL score, Liu et al., noted that “N” or nearness to the collecting system was the only RENAL score component significantly associated with complications after RAPN and LPN [47].
Conclusions RAPN is a safe treatment modality that expands the application of minimally invasive surgery allowing the extirpation of more technically challenging renal masses compared to traditional laparoscopic surgery. As the experience with RAPN has grown, studies demonstrate a similar incidence and complication profile compared to LPN. While robotic surgery provides distinct technical advantages, including stereoscopic vision, improved articulation of instruments and fine movement, surgeon experience continues to be the greatest factor in reducing complications. The most common complication is bleeding, while the risk of a urine leak and renal failure are far less common. Renal tumor grading systems standardize the descriptive language of renal masses and allow a more accurate comparison of outcomes and complications. Future studies will continue to assess the ability of these grading systems to predict complications and allow continued refinement and understanding of robotic renal surgical techniques. Compliance with Ethics Guidelines Conflict of Interest Dr. Eric Kim, Dr. Jeffrey A. Larson, Dr. Michael Figenshau, and Dr. R. Sherburne Figenshau reported no potential conflicts of interest relevant to this article. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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KIDNEY DISEASES (G CIANCIO, SECTION EDITOR)
Perioperative Complications of Robot-Assisted Partial Nephrectomy Eric H. Kim & Jeffrey A. Larson & Michael Figenshau & R. Sherburne Figenshau
Published online: 17 December 2013 # Springer Science+Business Media New York 2013
Abstract The incidence of renal cell carcinoma continues to increase with utilization of diagnostic abdominal imaging with migration towards a proportionally greater detection of small renal masses (SRM). Robot-assisted partial nephrectomy (RAPN) has become an attractive minimally invasive treatment modality for SRM’s due to the technical advantages and shortened learning curve compared to laparoscopic partial nephrectomy (LPN) while preserving comparable perioperative outcomes. With advances in ablative approaches for stage I renal cell carcinoma (RCC) and controversy surrounding the role of extirpative surgery for SRM’s, systematic understanding of the complications associated with RAPN has become even more imperative. This review aims to summarize and evaluate the contemporary literature, compile reported intraoperative complications, describe conventional and nephronsparing surgery (NSS) specific postoperative complications, and assess factors associated with an increased likelihood for perioperative complications following RAPN. Keywords Robot-assisted partial nephrectomy . RAPN . Robotic partial nephrectomy . Partial nephrectomy . Nephrectomy . Nephron-sparing surgery . NSS . Partial nephrectomy complication . Laparoscopic partial nephrectomy complication . Minimally-invasive complication . Da Vinci This article is part of the Topical Collection on Kidney Diseases E. H. Kim : J. A. Larson : M. Figenshau : R. S. Figenshau (*) Division of Urologic Surgery, Washington University School of Medicine, 4960 Children’s Place, Campus Box 8242, Saint Louis, MO 63110, USA e-mail: [email protected]
Introduction Due to the increased utilization of diagnostic abdominal imaging in recent years, the incidence of renal cell carcinoma (RCC) continues to increase. The American Cancer Society predicts 65,150 new RCC cases and 13,680 RCC deaths in the United States in 2013 [1]. There has also been proportionally greater detection of stage I disease and migration towards smaller tumor size within this stage [2]. In light of evidence that nephron-sparing surgery (NSS) provides favorable oncologic outcomes [3] and that radical nephrectomy (RN) is associated with significant morbidity and mortality [4], the American Urological Association (AUA) guidelines currently recommend partial nephrectomy (PN) as the standard of care for T1a tumors and as an alternative treatment for T1b tumors [5]. Robot-assisted partial nephrectomy (RAPN) has become a wide spread NSS modality because of the shortened learning curve compared to laparoscopic partial nephrectomy (LPN) [6] while achieving comparable perioperative outcomes [7]. With advances in ablative approaches for stage I RCC and recent controversy surrounding the role of extirpative surgery for small renal masses, systematic understanding of the complications associated with RAPN has become even more imperative. This review aims to summarize and evaluate the contemporary literature; compile reported intraoperative complications; describe conventional and NSS-specific postoperative complications; and assess factors associated with an increased likelihood for perioperative complications following RAPN.
E. H. Kim e-mail: [email protected]
Contemporary Series
J. A. Larson e-mail: [email protected]
As experience with RAPN has grown, studies successively updating single and multi-institutional perioperative complication rates of RAPN have been published. Table 1 summarizes contemporary studies with greater than 100 RAPN cases
M. Figenshau e-mail: [email protected]
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and their associated perioperative complication rates. In studies where complications were not categorized by ClavienDindo grade [8], we have attempted to do so based on the information provided. Although some more recent studies likely incorporate data from previously published reports, eliminating this redundancy was not feasible or substantively illustrative. Overall, RAPN is safe with reported intraoperative complication rates ranging from 1.4 % to 2.9 %, Clavien grade 1-2 postoperative complication rates ranging from 3.1 to 22.5 %, and Clavien grade 3-4 postoperative complication rates ranging from 2.0 % to 10.4 % [9••, 10–16]. Only one perioperative mortality occurred among all of the published studies [15]. Tanagho et al., have published the largest series to date with 886 patients included in their analysis. They report an intraoperative complication rate of 2.6 %, conversion rate of 0.8 %, and major (Clavien >3) postoperative complication rate of 3.6 % [9••]. This study is representative of the collection of contemporary series in Table 1. Generally, intraoperative complications are few, with intraoperative conversion to RN or to non-robotic PN even fewer. Additionally, minor postoperative complications (Clavien 1 and 2) were more common than major postoperative complications (Clavien 3 and 4). Death (Clavien 5 complication) in the postoperative period following RAPN was exceedingly rare. Conversion to other PN techniques and conversion to RN were not considered to be intraoperative complications by some authors. Spana et al., reported eight intraoperative complications, although they also reported six conversions to robotic RN that were not included as complications [12]. Scoll et al., and Rogers et al., report conversion rates to non-robotic PN modalities without specific mention of intraoperative complication rates [15, 16]. The seemingly broad range among postoperative complication rates are likely a result of under-reporting on the part of some studies. In studies where postoperative complications were not specifically categorized by Clavien grade, minor and clinically insignificant complications were likely omitted. This is evidenced by the reported Clavien grade 1-2 complication rates ranging from 3.1 to 22.5 %, depending on the study. Additionally, standardized definitions across all studies did not exist for all minor complications.
Intraoperative Complications Intraoperative complications of RAPN include vascular and visceral injury from laparoscopic access as well as hemorrhage and injury to adjacent structures, which may require conversion to laparoscopic, open, or radical nephrectomy. Access to the peritoneal cavity or retroperitoneal space with insufflation is necessary to achieve a working area for robotic surgery. Several techniques used to achieve
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laparoscopic access include classic pneumoperitoneum (Veress needle), open (Hasson) entry, direct trocar insertion, radially expanding trocars, and visual entry systems. Minor complications associated with access include extraperitoneal insufflation and skin or subcutaneous bleeding. Major complications include vascular or gastrointestinal injury as well as bladder, ureteral or solid organ perforation. A meta-analysis of laparoscopic entry techniques found vascular injuries to occur in 0.1 % and bowel injuries in 0.18 % of cases [17•]. Many retrospective and randomized controlled trials have attempted to identify the safest method of laparoscopic access. The updated meta-analysis of 28 randomized control trials with 4860 patients evaluating the various methods of access showed no advantage of any technique in preventing major complications [17•]. Using an open entry technique did reduce the incidence of failed entry, extraperitoneal insufflation, and omental injury but did not demonstrate lower vascular or visceral injury rates. Although RAPN is safe, the largest studies (Table 1) reported an intraoperative hemorrhage in 18 patients out of 2118 cases (0.8 %). The described causes are renal veinotomy, injury to the inferior vena cava (IVC), trocar injury to the inferior mensenteric artery (IMA), splenic laceration and renal hemorrhage from an unidentified unclamped renal artery. Likewise, injury to adjacent structures including bowel, spleen, liver, and pancreas was reported in five patients (0.2 %). Conversion to traditional laparoscopic partial nephrectomy (PN) or radical nephrectomy (RN )is also a rare event, reported in only 19 patients (0.8 %). Conversions were required for a wide variety of reasons including positive surgical margins, satellite lesions, perinephric scarring, indeterminate ultrasound tumor localization, and an endophytic tumor not amenable to NSS.
Postoperative Complications Conventional Many of the postoperative complications following RAPN are not unique to kidney surgery or use of robotic techniques. These conventional postoperative complications can be separated broadly into potentially life threatening and non-life threatening. The common non-life threatening complications following RAPN include gastrointestinal, pulmonary, and wound-related complications. Tanagho et al., Spana et al., and Rogers et al. ,have reported similar rates of ileus after RAPN: 1.2 % (11/886), 1.1 % (5/450), and 2.0 % (3/148), respectively [9••, 12, 16]. Many other contemporary studies, however, do not list ileus as a postoperative complication. The significantly decreased rate of ileus following laparoscopic
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Table 1 Summary of RAPN perioperative complications by study Study
Number of patients
Years enrolled
Intraop. complication rate
Conversion to PN (non-RAPN)
Conversion to RN
Postop. complication rate Clavien 1-2
Clavien 3-4
Clavien 5
Tanagho et al., 2013 [9••]
886
2007-2011
2.6 %
0.3 %
0.5 %
12.1 %
3.6 %
0%
Mathieu et al., 2013 [10] Ficarra et al., 2012 [11] Spana et al., 2011 [12] Kaouk et al., 2011 [13] Benway et al., 2010 [14] Scoll et al., 2010 [15] Rogers et al., 2008 [16]
240 347 450 252 183 100 148
2009-2011 2008-2010 2006-2009 2007-2010 2006-2008 2007-2009 2002-2007
n/a 2.9 1.8 2.0 2.7 n/a n/a
n/a 0% 0.7 % 2.0 % 1.1 % 1.0 % 1.4 %
n/a 0.6 % 1.6 % 0% 0% 1.0 % 0%
22.5 % 8.9 % 12.0 % 16.7 % 3.8 % 7.0 % 6.8 %
10.4 % 2.9 % 3.8 % 2.4 % 3.3 % 5.0 % 2.0 %
0% 0% 0% 0% 0% 1.0 % 0%
% % % %
intraop. = intraoperative, PN = partial nephrectomy, RN = radical nephrectomy, postop. = postoperative
approaches to nephrectomy, likely a result of decreased narcotic pain medication requirement and early ambulation, have been previously reported [18]. The same benefit is likely afforded to robotic approaches to nephrectomy. Non-life threatening pulmonary complications following RAPN, including dyspnea, atelectasis, pulmonary edema, and pneumonia, occurred at similar rates to ileus. Tanagho et al., Spana et al., and Kaouk et al., report these pulmonary complication rates as 1.4 % (12/886), 1.3 % (6/450), and 0.4 % (1/252), respectively [9••, 12, 13]. Wound-related complications, including local infection and hernia, occurred even less frequently. Tanagho et al., Spana et al., Kaouk et al., and Benway et al., report wound-related complication rates of 0.8 % (7/886), 0.7 % (3/450), 0.8 % (2/252), and 0.5 % (1/ 183), respectively [9••, 12–14]. Overall, the conventional nonlife threatening postoperative complications common to most abdominal surgeries occur at a relatively low frequency following RAPN. Thrombosis and cardiovascular events comprise the majority of potentially life-threatening postoperative complications common to abdominal surgery. Although urologic patients are typically of advanced age, cardiovascular postoperative complications following urologic surgery are relatively few compared to other surgical series [19]. Furthermore, cardiovascular events including arrhythmia and myocardial infarction (MI) are rare following RAPN. Tanagho et al., reports MI in 0.1 % (1/886) and arrhythmia in 0.5 % (4/886) of patients [9••]. Ficarra et al., reports MI in 0.3 % (1/347) and arrhythmia in 1.2 % (4/347) of patients [11]. Multiple studies including those by Spana et al., Kaouk et al., and Mathieu et al., report no occurrences of postoperative MI. Only one fatal postoperative MI is reported among the contemporary studies, occurring in the operating room during port site closure [15]. Likely the low cardiovascular complication rate of RAPN reflects the largely elective nature of the surgery, as the majority of tumors treated with RAPN are low stage [13–16].
The risk of thrombosis and thromboembolic complications following laparoscopic surgery has been well documented [20]. Although prevention strategies have diminished the incidence of postoperative thrombosis after urologic laparoscopic surgery [21], the risk of thromboembolic complications after RAPN is not negligible. For instance, pulmonary embolism was reported in 0.6 % (5/886), 1.6 % (7/450), 1.2 % (3/ 252), 2.0 % (2/100), and 1.4 % (2/148) of patients in contemporary series [9••, 12, 13, 15, 16]. Specific to Nephron-Sparing Surgery Although RAPN provides some technical benefits over LPN, the NSS-specific postoperative complications are common to both modalities [7, 22]. Specifically, these include bleeding complications requiring transfusion and/or additional procedures, urinary leakage as a result of collecting system violation, renal injury possibly related to warm ischemia time, and rarely, port-site metastases. Some of these NSS-specific complications are summarized in Table 2. Bleeding represents the most common postoperative complication following RAPN [9••, 10–16]. Postoperative bleeding complications following RAPN, including hematoma, hemorrhage, and pseudoaneurysm, ranged from 0.7 % to 12.3 % dependent on study [9••, 10–16]. Detection of postoperative hemorrhage is often driven by clinical presentation and confirmed by serial laboratory monitoring. As the larger series included in Table 2 show, postoperative bleeding requiring transfusion occurred in roughly 4 % of cases (4.2 % Tanagho et al., 3.7 % Ficarra et al., 4.2 % Spana et al.) [9••, 11, 12]. Postoperative transfusion rates following LPN are similar, with large studies reporting rates of 2.7 % and 4.5 % [23, 24]. Postoperative transfusion rate was substantially higher in the series reported by Kaouk et al., at 11.5 % [13]. Presumably, this represents a difference in transfusion criteria by institution rather than a difference in clinically significant bleeding.
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Table 2 Summary of NSS-specific postoperative complications following RAPN by study Study
Number of patients
Bleeding
Requiring transfusion
Pseudoaneurysm
Urine leak
Renal failure
Requiring hemodialysis
Tanagho et al., 2013 [9••] Mathieu et al., 2013 [10] Ficarra et al., 2012 [11] Spana et al., 2011 [12]
886 240 347 450
5.8 8.3 5.2 5.6
4.2 % n/a 3.7 % 4.2 %
1.1 3.8 1.4 0.2
%* % %* %
1.1 1.3 0.6 1.6
% % % %
0.7 % n/a 0% 0.2 %
0.2 % n/a 0% n/a
Kaouk et al., 2011 [13] Benway et al., 2010 [14] Scoll et al., 2010 [15] Rogers et al., 2008 [16]
252 183 100 148
12.3 % 3.8 % 3.0 % 0.7 %
11.5 % 1.1 % 3.0 % 0%
0.8 %* 1.6 % 1.0 % 0%
1.6 1.1 2.0 1.4
% % % %
0.8 % 0% 0% 0%
0.4 % 0% 0% 0%
% % % %
*bleeding requiring angioembolization was used as a surrogate for pseudoaneurysm
Although renal pseudoaneurysm following PN is traditionally considered a rare complication [25], it is more strongly associated with minimally invasive PN [26]. Reported rates of pseudoaneurysm following RAPN ranged from 0.2 % to 3.8 % depending on the study [9••, 10–16]. Although pseudoaneurysm was not specifically mentioned by Tanagho et al., Ficarra et al., and Kaouk et al., delayed hemorrhage requiring angioembolization was considered a surrogate. Typically, renal pseudoaneurysm presents as delayed gross hematuria and is associated with the treatment of centralized tumors [26, 27]. The gold standard for diagnosis and treatment of renal pseudoaneurysm remains selective angiography and embolization. Postoperative urinary leakage occurs as a result of collecting system violation during tumor excision and is specific to PN. Clinically, urine leak following RAPN may present as ileus, abdominal distention, electrolyte derangement, or increased surgical drain output. When no percutaneous drain was placed intraoperatively, management requires procedural intervention, such as ureteral stent, percutaneous drain, or percutaneous nephrostomy. Reported rates of urine leak following RAPN ranged from 0.6 % to 2.0 % depending on study [9••, 10–16], which was similar to reported urine leak rates following LPN in two large studies (1.9 % and 2.0 %) [23, 24]. Extrapolating from LPN studies, urine leak after RAPN is likely more common following resection of larger and deeper tumors [28, 29]. All of the reported urine leakage complications were successfully managed with percutaneous or ureteral drainage and did not require renal re-operation [9••, 10–16]. Reported rates of postoperative renal insufficiency were overall low, ranging from 0 % to 0.8 % depending on the study [9••, 11–16]. Although standardized definitions of postoperative renal insufficiency based on objective measures such as change in urine output or serum creatinine were not given, clinically significant postoperative renal insufficiency requiring hemodialysis was correspondingly low, ranging from 0 % to 0.4 % depending on the study [9••, 11, 13–16].
The decreased incidence of renal failure following RAPN may be a result of diminished warm ischemia time (WIT) as compared to LPN [7]. Higher WIT has been associated with renal functional deterioration following PN in the short and long term [30]. However, given that functional outcomes after PN are also strongly correlated to non-modifiable factors such as amount of renal parenchyma excised and baseline renal function [31, 32], the decreased incidence of renal failure following RAPN may represent patient selection. Port-site metastasis (PSM) is an exceedingly rare complication of laparoscopic oncologic surgery. The most recent review of the literature on renal cell carcinoma PSM reports nine previous cases following laparoscopic RN or PN and the first instance of renal cell carcinoma PSM following RAPN. Confirming previous reviews, the review states that contributing factors to PSM occurrence include patient immunosuppression, biologic aggressiveness of the tumor, and techniquerelated factors such as specimen morcellation and failure to use an entrapment bag [33].
Factors Predictive of Complications As expected with any surgical approach, perioperative outcomes improve with increased surgeon experience. Mottrie et al., demonstrated that progression of the surgeon learning curve was associated with decreased WIT, total operative time, and estimated blood loss (EBL) [34]. The improvement in perioperative measures with increased experience translates to decreased perioperative complication rate, as surgeons new to RAPN are likely to experience twofold to threefold higher complication rates. Mathieu et al. and Ficarra et al. demonstrated that the hazard ratio for perioperative complications was 2.14 and 2.99 for the first 20 and 30 cases in a surgeon's experience, respectively [10, 11]. Although increasing surgeon experience diminishes the risk, non-modifiable baseline patient characteristics also contribute to the likelihood of perioperative complications. Often
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advanced age is used as a surrogate for baseline comorbidity and is assumed to correlate with complication risk. However, Hillyer et al., demonstrated in a matched cohort study that age greater than 70 years does not correlate with an increased risk of perioperative complications [35]. Patient body-mass index (BMI) provides a rough measure of baseline comorbidity and increases the technical difficulty of RAPN and may predispose the patient to more complications [36]. However, multiple studies have demonstrated no significant association between perioperative complications and BMI for patients undergoing RAPN. Naeem et al., demonstrated no significant difference in complications between patients based on BMI less than or greater than 30 kg/m2 [37]. Kiziloz et al., and Isac et al., found no significant difference in complications when patients were further sub-stratified into categories based on ranges of BMI [38, 39]. However, all three studies demonstrated a significant association between higher BMI and increased EBL [37–39]. Gorin et al., may have clarified the distinction by demonstrating that BMI and outer abdominal fat are not associated with increased complication rate, whereas increasing intraabdominal fat is significantly associated with complications [40]. Recently developed grading systems for renal tumors considered for PN include the RENAL nephrometry score [41] and PADUA classification [42]. Both grading systems have been validated as independent predictors of complications following PN, with four times greater odds of complication when the RENAL score is 9 or greater and when the PADUA classification is 10 or greater [43]. Specific to RAPN, increasing RENAL score appears to be associated with higher overall complication rates and major complication rates. Tanagho et al., found that in patients undergoing RAPN, RENAL scores of 4-6, 7-9, and 10-12 resulted in complication rates of 11, 18, and 23 %, respectively [9]. Simhan et al., found that, in patients undergoing PN, of which roughly half underwent RAPN, RENAL scores of 4-6, 7-9, and 10-12 resulted in major complication rates of 6, 11, and 22 %, respectively [44]. Nevertheless, the RENAL score may not be a strong predictor of complications following RAPN, as the correlation found by Tanagho et al., was small (OR=1.18) and other studies have found no significant association between RENAL score and RAPN perioperative complications [9••]. Similarly, PADUA classification has been found to be a significant but weak predictor of complications following RAPN (OR=1.04) [11]. The decreased strength of correlation between anatomic renal tumor grading systems and complications for patients undergoing RAPN as compared to LPN or OPN may be a result of increased surgeon experience as well as a technical advantage of robotic approaches to PN. Additionally, individual components of the RENAL score and PADUA classification have been examined for association with complication rates. Patel et al., demonstrated that the
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distinction between tumors equal to or less than 4 cm (stage T1a) and tumors greater than 4 cm did not predict occurrence of a perioperative complication after RAPN [45]. Both Tanagho et al., and Ficarra et al., demonstrated that tumor size, when evaluated as a continuous variable, has a small but statistically significant correlation to perioperative complications after RAPN [9••, 11]. Although the increased difficulty of renal dissection in the case of hilar tumors seems apparent, Dulabon et al., found that hilar tumor location was not significantly associated with complications after RAPN [46]. Other studies have demonstrated that tumor proximity to the collecting system is the characteristic most strongly correlated to complication rates, likely as a result of increased collecting system violation and associated sequela. Mathieu et al., found that collecting system violation had a threefold higher association with major complications [10]. While evaluating the RENAL score, Liu et al., noted that “N” or nearness to the collecting system was the only RENAL score component significantly associated with complications after RAPN and LPN [47].
Conclusions RAPN is a safe treatment modality that expands the application of minimally invasive surgery allowing the extirpation of more technically challenging renal masses compared to traditional laparoscopic surgery. As the experience with RAPN has grown, studies demonstrate a similar incidence and complication profile compared to LPN. While robotic surgery provides distinct technical advantages, including stereoscopic vision, improved articulation of instruments and fine movement, surgeon experience continues to be the greatest factor in reducing complications. The most common complication is bleeding, while the risk of a urine leak and renal failure are far less common. Renal tumor grading systems standardize the descriptive language of renal masses and allow a more accurate comparison of outcomes and complications. Future studies will continue to assess the ability of these grading systems to predict complications and allow continued refinement and understanding of robotic renal surgical techniques. Compliance with Ethics Guidelines Conflict of Interest Dr. Eric Kim, Dr. Jeffrey A. Larson, Dr. Michael Figenshau, and Dr. R. Sherburne Figenshau reported no potential conflicts of interest relevant to this article. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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