Prevention and Handling of Complications of Renal Focal Therapies

Introduction

T he last few decades have seen a well-documented shift in presentation of renal-cell carcinoma toward small, asymptomatic tumors. ¹ This shift also seems to confer a change in the biologic nature of the lesions that are encountered. Thus, rather than dealing with the most lethal urologic cancer, we are now often presented with a low-risk lesion in an increasingly elderly population.

With the oncologic risk substantially lowered, the acceptable level of morbidity for treatment is also reduced. Of small renal masses (SRMs), 20% to 30% are considered benign or indolent and thus may not necessitate intervention. ^2,3 Surveillance programs, using serial imaging with or without renal biopsy, can allow the patient to avoid treatment-associated morbidity. ⁴ Contemporary series have shown renal biopsy to be safe and accurate in this setting. ^5,6 In patients with an SRM, when intervention is deemed necessary, careful case selection is vital to deliver the low levels of treatment-related morbidity that are considered acceptable.

Both radiofrequency ablation (RFA) and cryoablation (CA) are in clinical use, but high-intensity focused ultrasound (HIFU) remains experimental. As such, HIFU has little morbidity data available and is not considered in this review. In addition to the nature of the ablative technology itself, the method of delivery is important in terms of the complication profile. RFA has tended to be delivered via the percutaneous approach, whereas CA has been used both percutaneously and laparoscopically.

Damage to Related Structures

A major consideration in deciding the most appropriate treatment modality for an SRM is its position and size. Potentially, any of the structures that surround the kidney can be damaged, but clinical complications are most frequently seen in relation to the bowel, pelvicaliceal system, or ureteral injury.

In general, laparoscopic approaches are considered advantageous in cases in which the area of tissue ablation puts surrounding structures at risk. Mobilization of the kidney allows the SRM to be isolated from related structures, and the tumor ablation can be monitored under direct vision, with concurrent use of laparoscopic ultrasound and temperature probes. This mobilization can also allow ablation of lesions in positions that are hard to target percutaneously but can itself lead to damage to surrounding structures.

In the percutaneous setting, a degree of dissection is also possible. Fluid or gas can be injected between the area to be ablated and the related structure to separate them. ⁷ This is most frequently used to distance the colon from an anteriorly positioned SRM. While this technique increases the proportion of SRMs that can be treated percutaneously, certain structures, such as the ureter, are less easy to protect in this way. Most practitioners would consider proximity to the ureter a contraindication for percutaneous treatment, although some have used retrograde pyeloperfusion with good effect. ⁸ The proximity of the SRM to the renal vasculature also needs to be considered. Renal blood flow can lead to insufficient tissue heating or cooling and thus incomplete ablation. Thus, for SRMs close to the hilum, a laparoscopic approach may be advantageous. Care must also be taken with regard to the nerves of the posterior abdominal wall and the pleura. Ablation of lesions close to the adrenal gland can rarely lead to acute hypertensive crisis or adrenal insufficiency where the contralateral adrenal is non-functioning. ⁹

The treatment of collateral damage relies on early diagnosis, which is in turn dependent on careful postoperative evaluation with timely and appropriate use of imaging. Detecting complications can be difficult, because they are relatively infrequent and nonspecific in their presentation. Common warning signs include unexplained tachycardia, low-grade fever, and abdominal discomfort or distension. Any divergence from the expected postoperative course should be considered to represent a potential complication. In addition to clinical evaluation, CT scanning is useful in evaluating these persons, with oral and intravenous contrast enhancement adding to the diagnostic usefulness of the test.

When bowel injury is found or suspected, early involvement of a gastrointestinal surgeon is advisable. In cases of damage to the pelvicaliceal system or ureter, ureteral stent placement is often effective.

Hemorrhage

Negating the need for renal vessel cross-clamping together with the reduced incidence of hemorrhage are considered advantages of focal therapies over partial nephrectomy. ¹⁰ When it does occur, hemorrhage can be caused by damage to surrounding vascular structures but is more frequently seen from the SRM itself.

The risk of hemorrhage is increased when coagulation or platelet function is impaired. Where this bleeding diathesis is seen as a result of medication, the risks of stopping the drug must be weighed against the increased risk of hemorrhage if it is continued. This decision can be difficult for patients who are treated with clopidogrel, particularly after coronary artery stent placement. Consultation with a cardiologist is advised and, on occasion, the patient may be best served by deferring the procedure until the risk of stopping the clopidogrel decreases.

During cryotherapy, care must be taken not to move the cryoprobes until the treatment area has thawed. Probe movement in frozen tissue can induce tissue fracture with resulting hemorrhage. When this is encountered in the laparoscopic setting, the initial management is with application of direct pressure. Additional measures include the use of an absorbable hemostat or hemostatic sealant. When assessing the effectiveness of hemostatic intervention, it is important to consider the patient's blood pressure and reduce the insufflation pressure.

When hemorrhage is encountered postoperatively, treatment is determined by whether the hemorrhage is considered to be active. In patients who are hemodynamically stable or respond to initial intravenous fluid challenge, perinephric hematomas are usually self-limiting and can be managed conservatively. In situations in which hemorrhage is ongoing, the patient should be fluid resuscitated, and hematologic parameters should be optimized. The imaging modality will depend on patient stability and the intervention contemplated but will most frequently involve contrast-enhanced CT or angiography. When interventional radiology is available, most urologists would consider embolization as first-line treatment; otherwise surgical exploration is indicated.

Comparison of Complications for the Different Ablation Modalities

There are currently no studies that have randomized patients to treatment with the different ablative techniques. When comparing morbidity between the ablative modalities, it is difficult, therefore, to determine whether the differences relate to the technology or nature of the cases that were treated.

Table 1 shows the outcomes from both laparoscopic and percutaneous CA together with percutaneous RFA, as described in a recent review of the literature. ¹¹ Major intraoperative complications were encountered in 4% of laparoscopic cryoablation cases as opposed to a single major anesthetic complication seen in 530 percutaneous RFAs and CAs. The laparoscopic intraoperative complications consisted mainly of hemorrhage secondary to tissue fracture and conversion to open procedures. With increasing experience, it would seem likely that the rate of these laparoscopic complications could be reduced.

Rates of major postoperative complications were similar between percutaneous and laparoscopic approaches, seen between 4% and 6% of cases. Ureteral injury was more than twice as common in the RFA group as the cryoablation groups (percutaneous and laparoscopic) but still infrequent at 1.6% of RFA cases. ¹¹

The morbidity rates also need to be taken in context of the incomplete ablation and tumor recurrence rates. These were less than 3% for the laparoscopic cryoablation group but 7.5% for percutaneous CA and 12% for percutaneous RFA. ¹¹

A prospective, multicenter trial has looked at perioperative negative outcomes after laparoscopic cryoablation. Negative outcomes were seen in 15% of patients, but 80% of these were considered minor. Risk factors for negative outcomes were preexisting cardiac conditions, female sex, and tumor size. The authors considered tumor size of more than 3.4 cm to be the cutoff for increased risk of negative outcome. ¹²

A high risk of bleeding from laparoscopic cryoablation from larger tumors (>3 cm in diameter) has also been reported by Hruby and coworkers. ¹³ This risk may be particularly high for large peripheral tumors with the use of multiple modern needles, which can induce fractures by their rapid freezing. More centrally located tumors are less prone to capsule fracture because of the insulating effect of surrounding renal tissue.

Conclusions

The ablative techniques considered are associated with relatively low morbidity rates. Complications can be minimized by careful case selection and attention to surgical technique. Percutaneous techniques seem to be associated with lower morbidity but higher recurrence rates and should probably be avoided in SRMs located close to the ureter or hilum. The higher morbidity associated with laparoscopic cryoablation most often relates to hemorrhage of the renal capsule in peripheral tumors more than 3 cm in diameter, which may be mitigated by reducing the rate of freezing.

Failure of the patient to make the expected recovery after the procedure should be regarded as a potential complication, even when symptoms are nonspecific. In these cases, serial observation with the judicious use of CT will allow for early detection and management of complications.