Abstract
Renal mass ablation is increasingly more common as long-term oncologic outcomes have shown comparability to nephron-sparing extirpative surgery, with less morbidity. Patient selection plays the largest role with respect to minimizing complications. In managing complex ablations adjunct procedures, including preoperative embolization, hydrodisplacement, and retrograde pyeloperfusion, can potentially lower complication rates.
Although radiofrequency and cryoablation are the best-studied modalities, the emergence of microwave ablation and irreversible electroporation has recently been seen. The most common major complication after heating modalities (radiofrequency or microwave ablation) is urinary tract injury, while hemorrhage is the most common major complication after cryoablation. Irreversible electroporation is a nonthermal modality, and fewer studies limit our full understanding of complications.
This chapter focuses on prevention of complications, followed by specific complications associated with each modality. Finally, we review management of major ablation complications.
Keywords
Complications, Thermal ablation, Radiofrequency ablation, Cryoablation, Microwave ablation, Irreversible electroporation
Chapter Outline
Managing Complications of Ablation
[CR]
Key Points
- 1.
Ablation therapy is being used with increasing frequency for renal masses.
- 2.
Complication rates of renal mass ablation compare favorably to extirpative nephron-sparing surgery.
- 3.
Patient and tumor selection are the most important factors to prevent complications.
- 4.
The most common complications after percutaneous renal mass ablation are minor and include pain or paresthesia and asymptomatic hematomas.
- 5.
Urinary tract injury is the most common major injury after radiofrequency or microwave ablation and is often managed with ureteral stenting or percutaneous drains.
- 6.
Hemorrhage is the most common major injury after cryoablation. Larger tumors can be embolized preoperatively to limit the risk of hemorrhage.
Introduction
With the rise in diagnosis of incidental small renal masses, a shift in management of renal cell carcinoma (RCC) has emerged. Most notable is the increased utilization of nephron-sparing techniques. A recent publication based on the National Inpatient Sample showed that from 2005 to 2007 there was a 25% and 20% relative increase in the use of thermal ablation (TA) and partial nephrectomy (PN), respectively, while the use of radical nephrectomy (RN) had a 7% relative decrease.
In 2009, the American Urological Association’s (AUA) Guideline for the Management of the Clinical Stage 1 Renal Mass stated that for T1a renal lesions PN and RN are considered a standard of care (highest grade). TA is considered an option (lowest grade) for healthy patients and a recommendation (middle grade) for unhealthy patients. This conclusion, appropriate at the time of publication, stemmed from outcomes with increased risk of local recurrence and shorter follow-up. More recent publications have improved our understanding of TA outcomes.
Psutka et al. reviewed 185 patients with cT1 RCC undergoing percutaneous radiofrequency ablation (RFA), with a median follow-up of 6.4 years. They demonstrated 5-year cancer-specific survival (CSS) of 99% and local recurrence-free survival (LRFS) of 95%. Evaluating laparoscopic cryoablation (CA), 142 patients with cT1 RCC and a median follow-up of 92 months had 5-year CSS of 97% and LRFS of 87%. Given the indolence of many of the tumors, the CSS survival data are not surprising considering what we know about active surveillance in this population. More important, however, is the focus on local control. More recent studies, specifically focused in the RFA literature, have demonstrated that with refined preoperative tumor selection we can improve LRFS outcomes to approach those of partial nephrectomy. With longer follow-up and improved oncologic outcomes, we anticipate increased utilization of ablative techniques in the management of renal masses. Therefore a thorough understanding of complications is critical to achieving excellent oncologic efficacy while minimizing morbidity.
Based on the aforementioned 2009 AUA Guideline, the morbidity of RFA and CA compares favorably with that of laparoscopic PN (LPN), a referent standard, in the context that LPN patients had similar sized tumors and were younger and, presumably, healthier. To understand in further detail, the following chapter reviews the mechanism of action of ablative technologies, along with the prevention, frequency, and management of complications. Although RFA and CA are the most popular modalities used, newer modalities, including microwave ablation (MWA) and irreversible electroporation (IRE), are also discussed.
Prevention of Complications
Many factors play into complication risk during and after ablation. Most important is choosing appropriate patients who have a high probability of success with a low risk of complications. However, there are instances where higher-risk patients or tumors have ablation as a solitary option. In this scenario adjunct procedures, such as preoperative angioembolization, hydrodisplacement, and cold pyeloperfusion can help minimize complications.
Patient Selection
Patient selection plays the largest role in preventing complications. While it is generally understood that larger tumors, tumors closer to renal sinus, and tumors close to important structures are most at risk of complications, quantifying that risk can be difficult.
The RENAL nephrometry score (Radius, Exophytic/Endophytic, Nearness to the collecting system or sinus, Anterior/posterior and Location relative to polar lines) was developed to standardize renal tumor size, location, and depth and has been shown to correlate with complications after PN. Subsequent work by Schmit and colleagues compared RENAL nephrometry scores to complication rates in patients undergoing percutaneous ablation (RFA or CA). In 627 patients (751 tumors) there was a significant association between higher RENAL nephrometry score and major complication (≥Clavien III) risk, with low- (RENAL 4–6), moderate- (RENAL 7–9), and high-complexity (10–12) major complication rates of 3.4%, 5.4%, and 15.9%, respectively (p < 0.001). Overall, major complications occurred in 7.8% of CA, but only 2.7% of RFA. They did not do independent analysis on type of TA, and, therefore, their finding might be dominated by CA alone. Similar results correlating RENAL nephrometry score and CA complications were also confirmed in another series.
In contrast, Seideman et al. found no association between RENAL nephrometry score and risk of complications in 199 RFA procedures (2.0% Clavien grade III–IV). They argued that additional factors related to the type of TA could affect complication risk. For example, most CA probes and some RFA probes must puncture through the tumor, while the RFA probe used in their series deploys small 25G tines into the tumor, potentially minimizing trauma. Other potential reasons why no association was seen could be that the standard RENAL nephrometry score does not capture size differences between tumors that are generally <4 cm. A more discerning tool might be the modified RENAL nephrometry score, which has shown improved correlation with oncologic outcomes.
Specifically evaluating laparoscopic CA, Lagerveld et al. differentiated risk factors for both intraoperative and postoperative complications. They concluded that intraoperative complications are significantly associated with tumors >3.5 cm, which appears to predict complications better than RENAL nephrometry score. Regarding postoperative complications, only the N (nearness to collecting system) portion of the RENAL nephrometry score was predictive of complications.
Both RFA and CA can be used to treat exophytic as well as completely endophytic renal masses. Selection of the approach (laparoscopic versus percutaneous) depends on tumor location, patient’s health status, and the surgeon’s expertise. At our center, we use TA to treat tumors of <3–4 cm that typically have a peripheral component allowing percutaneous access. Laparoscopic or robot-assisted TA is rarely recommended. We believe the energy source chosen should be based on physician preference, and we solely use RFA given our comfort and experience with the modality. More endophytic tumors might have the benefit of ice ball monitoring with CA, although outcome differences have not been reported in the literature.
Historically, contraindications to percutaneous TA have included tumors adjacent to the renal pelvis or ureter, or near important structures (bowel, liver, spleen, etc.). However, more advanced work with hydrodisplacement has made these relative contraindications.
Preoperative Angioembolization
Initially described to minimize the heat-sink effect in RFA, preoperative tumor angioembolization has more recently been utilized to limit complications with CA. CA carries an increased risk of hemorrhage, especially in larger tumors, due to renal capsule fracture. In addition, unlike RFA, freezing of a tumor does not have inherent coagulative effects and likely causes a local coagulopathy with regard to platelet function. Woodrum and colleagues embolized 40% (4/10) of tumors ≥5 cm that underwent CA. The decision to undergo embolization was based on central involvement of the tumor, number of probes needed to treat the tumor, and tumor vascularity. There was no difference in mean tumor size between the embolization group (6.2 cm) and the no embolization group (5.7 cm, p = 0.26). Mean hematoma volume in patients who underwent preoperative embolization was 18 mL, compared to 357 mL in patients who did not (p < 0.001). Clinically, this translated into no blood transfusions in the embolization group, and one transfusion (17%) in the no embolization group. This study was retrospective and small, but certainly suggests that utilizing preoperative embolization in large tumors can decrease the risk of hemorrhage. Further work on embolization from the same institution shows increased utilization in larger tumors: 15% of cT1b patients and 58% of cT2 patients underwent preoperative embolization.
Similar results were found by Miller et al., who reviewed their small series of 21 tumors. Four tumors (mean 4 cm) were treated preablation with embolization and had no complications. In contrast, the remaining 17 tumors (mean 3.6 cm) had an 83% complication rate, including a 41% hemorrhage rate. Although their study lacked granularity with regard to blood transfusions, they concluded preablation embolization reduces the risk of hemorrhage.
We do not use angioembolization in our practice, as we prefer to treat larger tumors that might benefit from angioembolizaiton prior to CA with either partial or radical nephrectomy. If thermal ablation is performed in a larger tumor (>3–4 cm), we prefer to use RFA as it is coagulative, precluding the need for angioembolization.
Hydrodisplacement
All forms of TA risk injury to nearby structures, and it is generally accepted that structures within 1 cm of a renal lesion are most at risk. Colon is most commonly involved, but abdominal wall, small intestine, ureter, and psoas muscle are also encountered. Hydrodisplacement prior to ablation was first described by Farrell and colleagues, who used sterile water to displace bowel prior to RFA ( Fig. 23.1 ). This technique involves fine needle placement in a plane between the tumor and structure, with instillation of fluid. Typically, 5% dextrose or sterile water are used, although iodinated contrast material has been described to better illuminate the infusion on cross-sectional imaging. It is best to avoid saline if performing RFA due to the risk of ionic transmission of energy.
The type of thermal ablation should not affect the success of hydrodisplacement; studies have shown 96% success (50 of 52) prior to CA and 96% success (53 of 55) prior to RFA. More contemporary series have demonstrated that hydrodisplacement was used prior to 12–14% of RFA procedures. It is less frequently described in CA series, except in procedures involving large (cT1b/cT2) tumors, where it was used 35–42% of the time.
In our experience, tumors that lie in close proximity to critical structures often gain enough separation just by positioning the patient prone or lateral decubitus. Hydrodisplacement is infrequently needed, but often successful when used. We find the greatest success when displacing colon or small intestine. The ureter can be more difficult to move; tumors in close proximity to the ureter are more commonly referred for partial or radical nephrectomy.
Pyeloperfusion
For tumors that lie close to the ureter or collecting system, prior investigations have looked at retrograde ureteral infusion of cold fluid. The first description of this technique during RFA was by Wah and colleagues in 2005. They published a case report with retrograde infusion of 5% dextrose solution cooled to 6°C at a pressure of 80 cm of H 2 0 for a 2-cm centrally located tumor. The infusion was through a 7F pigtail catheter placed endoscopically into the renal pelvis and subsequently removed 48 hours after the procedure. Just as in hydrodisplacement, a nonionic solution was used due to theoretical concerns about energy transmission. The patient recovered well without any collecting system or ureteral damage.
They followed this initial investigation by publishing results of their pilot study, comprising 17 patients with 19 tumors that were within 1.5 cm of the ureter. No complications occurred, and no patients developed urinary fistulas or ureteral strictures. Although there is the potential to cause a heat sink with cold pyeloperfusion, there were no local recurrences during their follow-up period. The most recent series by Wah et al. utilized this technique in 6.2% (13/210) of RFA procedures.
Complications of Ablation
Radiofrequency Ablation
Radiofrequency ablation can be performed either laparoscopically or percutaneously. The main difference with respect to complications relates to the need to mobilize colon and/or small intestine and expose the tumor to perform the ablation laparoscopically. These portions of the procedure have expected risks that are no different than a laparoscopic radical or partial nephrectomy. Specifically related to the ablation portion of the procedure, most complications are related to thermal injury.
The 2009 AUA Guideline meta-analysis lists major urologic complications including hemorrhage requiring transfusion or other intervention, urinary leak or fistula, and loss of kidney function, among others. The major RFA complication rate was 6% (range 4.4–8.2%), not significantly different than CA. Comparing studies is often difficult due to different terminology, different grading criteria, and lack of granularity. A contemporary list of RFA studies with complications are summarized in Table 23.1 . Ranges for minor Clavien grade I complications, grade II complications, and major grade III–V complications were 5–19%, 1–8%, and 2–10%, respectively. Specific complications are discussed below.
| Study (year) | No. Patients/Procedures | Approach | Tumor Size (mean, cm) | Hydrodisplacement | Pyeloperfusion | Clavien I | Clavien II | Clavien III/IV | Blood Transfusion | Urinary Tract Injury |
|---|---|---|---|---|---|---|---|---|---|---|
| Iannuccilli et al. (2015) | 203/203 | Perc | 2.5 | 28 (13.8%) | – | 22 (10.8%) | 0 | 8 (3.9%) | 0 | 7 (3.4%) |
| McClure et al. (2014) | 84/115 | Perc | 2.6 | – | – | 11 (9.6%) | 1 (1.2%) | 3 (2.6%) | 1 (1.2%) | 2 (2.4%) |
| Lorber et al. (2014) | 53/53 | 29 Perc/ 24 Lap | 2.3 | – | – | 10 (18.9%) | 4 (7.5%) | 0 | – | – |
| Wah et al. (2014) | 165/210 | Perc | 2.9 | 26 (12.4%) | 13 (6.2%) | 12 (6.7%) | 0 | 9 (4.3%) | 0 | 7 (3.3%) |
| Ramirez et al. (2014) | 79/79 | Lap | 2.2 | – | – | 4 (5.1%) | 3 (3.8%) | 0 | 3 (3.8%) | |
| Seideman et al. (2013) | 199/199 | 170 Perc/ 29 Lap | 2.4 | – | – | 10 (5.0%) | 4 (2.0%) | – | – | |
| Balageas et al. (2013) | 62/62 | Perc | 2.3 (median) | – | – | – | – | 6 (9.7%) | 1 (1.6%) | 3 (4.8%) |
| Atwell et al. (2013) | 222/232 | Perc | 1.9 | – | – | – | 3 (1.3%) | 7 (3.0% | – | 4 (1.7%) |
| Atwell et al. (2012) | –/254 | Perc | 2.1 | – | – | 13 (5.1%) | 3 (1.2%) | 9 (3.5%) | – | 6 (2.4%) |
Mechanism of Action
Radiofrequency ablation uses a monopolar alternating electrical current using the frequency within the radio segment of the electromagnetic spectrum. The current flows between the grounding pad and the RFA probe. Heat is generated as a result of ionic agitation of the tissue around the probe, and cell death is achieved when the temperature within a tumor and a small rim of the surrounding tissue rises to 60°C. High temperatures produce occlusion of the microvasculature and destruction of the cellular cytoskeleton, causing tissue ischemia and impaired DNA replication, and ultimately resulting in a predictable zone of coagulation necrosis around the radiofrequency electrode.
During RFA tissue temperatures generally reach >100°C. In addition to causing cell death, heating also has inherent coagulant properties to limit the risk of hemorrhage.
Urinary Tract Injury
Typically, the most common major injury with RFA is to the urinary tract, either the collecting system or ureter ( Fig. 23.2 ). In a porcine model, Brashears et al. demonstrated that after causing direct damage to the collecting system, four of seven RFA procedures resulted in urinary fistula. In contrast, after 15 direct cryoablation procedures to the collecting system not a single fistula developed.
Although most urinary tract injuries lead to major complications, studies have described minor complications including a single episode of urine leak (0.9%) and two ureteral strictures (1.0%) managed conservatively. More commonly, injury to the urinary tract is a grade III complication as it requires either ureteral stenting or percutaneous drainage, and has been described in 1.7–4.8% of cases.
Hemorrhage
As stated before, the risk of bleeding after RFA is low given the coagulative properties of heating tissue. However, many studies describe minor Clavien grade I complications of perinephric hematoma after RFA ( Fig. 23.3 ) without subsequent transfusion, up to 14.5% of cases. More importantly, the need for blood transfusion (grade II) or subsequent angioembolization (grade III) is an infrequent event in most RFA series (0–1.6%).
Pain/Neuropathy
A common minor grade I complication after RFA is pain or neuropathy. Baker et al. noted the correlation between pain after RFA and distance of the renal tumor to body wall musculature. Reports of significant pain or nerve injury were made in most series, with the highest incidence in 3.9% of cases. However, as described in their report, 90% of these patients had resolution of their symptoms within 6 months.
Pneumothorax
Pneumothorax in RFA is typically either related to the probe traversing the pleural cavity, or diaphragmatic injury during laparoscopy. Seideman et al. described a single case of pneumothorax that required needle decompression (grade III, 0.5%), while most other series described minor grade I pneumothoraces that were managed conservatively (up to 4.8%).
Other
Damage to colon or small intestine are rare complications of RFA. In the contemporary studies listed, only one patient (1.6%) experienced a duodenal perforation, which was reported by Balageas et al.
Cryoablation
Like RFA, contemporary cryoablation (CA) is performed either laparoscopically or percutaneously, and complications due to laparoscopic CA are related to mobilization of the colon and nearby structures and exposure of the tumor. In this section, we focus on complications specific to the ablation itself.
The 2009 AUA Guideline meta-analysis lists major urologic complications from CA of 4.9% (3.3–7.4%), not significantly different than from RFA. Like RFA, major complications analyzed in this meta-analysis include hemorrhage requiring blood transfusion and/or interventions and urinary tract injury. With CA, and as many highlighted studies show, the most concerning complication is the risk of hemorrhage due to ice ball–induced renal capsule fracture and local coagulopathy.
A contemporary list of CA studies is listed in Table 23.2 . For the purposes of summarizing these findings, the 2015 studies by Atwell et al. and Moynagh et al. are excluded because of the size of the tumors treated being discordant from general practice. Minor grade I complications were reported in up to 11% of cases, while grade II complications were reported in 1–15% of cases. Major complications (Clavien grade III or IV) ranged from 1% to 5% in most series.
| Study (year) | No. Patients/Procedures | Approach | Tumor Size (mean, cm) | Preoperative Embolization | Hydrodisplacement | Clavien I | Clavien II | Clavien III/IV | Blood Transfusion | Urinary Tract Injury |
|---|---|---|---|---|---|---|---|---|---|---|
| Caputo et al. (2015) | 138/138 | Lap | 2.4 | -– | – | 8 (5.8%) | 2 (1.4%) | 5 (3.6%) | 3 (2.2%) | – |
| Atwell et al. (2015) | 46/46 | Perc | 4.8 | 7 (15%) | 16 (35%) | 1 (2.0%) | 3 (6.5%) | 4 | 2 (4.3%) | 0 |
| Moynagh et al. (2015) | 12/12 | Perc | 8.4 | 7 (58.3%) | 5 (42%) | 1 (8.3%) | 6 (50%) | 2 (16.7%) | 3 (25%) | 0 |
| Zargar et al. (2015) | 412/– | 137 Perc | 2.2 (median) | – | – | 9 (6.6%) | 0 | 1 (0.7%) | – | – |
| 275 Lap | 2.5 (median) | – | – | 8 (2.9%) | 7 (2.5%) | 5 (1.8%) | 7 (2.5%) | 1 (0.4%) | ||
| Larcher et al. (2015) | 174/– | Lap | 2.0 (median) | – | – | 16 (9.0%) | 25 (15%) | 5 (3%) | 14 (8.0%) | – |
| Kim et al. (2014) | 263/– | 145 Lap | 2.4 | – | – | 1 (0.7%) | 3 (2.1%) | 1 (0.7%) | – | |
| 118 Perc | 2.7 | – | – | – | 2 (1.7%) | 1 (0.8%) | 2 (1.7%) | 1 (0.8%) | ||
| Emara et al. (2014) | 56/56 | Lap | 2.6 | – | – | 3 (5.4%) | 1 (1.8%) | 1 (1.8%) | 0 | 1 (1.8%) |
| Atwell et al. (2013) | 163/176 | Perc | 2.3 | – | – | – | 4 (2.3%) | 5 (2.8%) | – | |
| Breen et al. (2013) | 147/153 | Perc | 3.3 | – | 75 (49%) | 9 (5.9%) | 1 (0.7%) | 6 (3.9%) | 1 (0.7%) | 3 (2.0%) |
| Blute et al. (2013) | 139/– | Perc | 2.4 | – | – | 15 (10.8%) | 3 (2.2%) | 0 | 0 | 0 |
| Atwell et al. (2012) | –/311 | Perc | 3.2 | 12 (3.9%) | – | 15 (4.8%) | 10 (3.2%) | 16 (5.2%) | 4 (1.3%) | 0 |
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