Abstract
Background
Microwave ablation (MWA) has been developed as one of the most commonly used local oncologic treatments. However, there is still a dearth of studies concerning MWA in the treatment of renal angiomyolipomas (AML).
Purpose
To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous MWA when treating AML.
Material and Methods
Nineteen lesions with pathologically confirmed AML in 14 patients (5 men, 9 women; mean age, 49.2 ± 14 years) were treated with US-guided percutaneous MWA with one or two cooled-shaft needle antennae. A power output of 45 W or 50 W for 300–1140 s was emitted to achieve complete tumor necrosis. Contrast-enhanced ultrasound (CEUS) was performed to observe the treatment efficacy 3 days later. Patients were followed up with CEUS, computed tomography (CT), and/or magnetic resonance imaging (MRI) after 1, 3, and 6 months, and long-term ablation efficacy was evaluated every 6 months thereafter.
Results
Among the 19 renal lesions, 17 achieved complete ablation as monitored by US after one session of MWA, and two patients required a second session of MWA. Postoperative evaluation with CEUS showed that complete ablation was obtained in 15 lesions; however, in four lesions, complete ablation could not be attained. During the follow-up period of 6–36 months (median, 10 months), a fistula to the descending colon was found in one patient and local infection around the ablation zone was found in another. Neither injury to the renal pelvis nor damage to renal function was observed. None of the patients exhibited hematuria or abnormalities in routine urine tests during the hospitalization period or during follow-up. Minor complications, such as subcapsular bleeding, mild to moderate pain, and fever were eliminated after appropriate treatment.
Conclusion
MWA is an effective and minimally invasive technique for the management of AML that can preserve renal function with acceptable complication rates.
Introduction
As the most common benign renal mesenchymal neoplasm, renal angiomyolipoma (AML) originates from perivascular epithelioid cells and contains a variable proportion of adipose tissue, smooth muscle, and blood vessels (1). It can occur as a stand-alone condition (approximately 70% of the time) or appear as a part of the tuberous sclerosis complex. Large renal AML (diameter > 3.5 cm) may cause symptoms such as flank pain, hematuria, and retroperitoneal hemorrhage. It is generally agreed that asymptomatic AMLs >4 cm and symptomatic lesions of any size should be treated (2–4).
For benign AMLs, renal-preserving treatment methods, including selective angioembolization (SAE) and nephron-sparing surgery (NSS), are preferred (5). Although angioembolization has been well-recognized as an effective treatment modality for acute retroperitoneal hemorrhage in patients under unstable conditions, it has been reported that bleeding or other persistent symptoms after embolization of AML occurs in 10–30% of patients (5) and that further embolization is required in 80% of patients (6). NSS has been well-accepted in patients with AML, but urine leakage (5.2%, 3/58), ileus (8.6%, 5/58), and proteinuria (13.8%, 8/58) are the most common complications (7). Currently, thermal ablative techniques have been embraced as primary treatment options for several malignancies, including hepatic, lung, and renal cancer. These techniques have been developed in an attempt to provide acceptable oncologic control while abating the morbidity associated with the partial nephrectomy (8,9). Our study group previously reported short-term results of ultrasound (US)-guided percutaneous microwave ablation (MWA) of 12 renal cell carcinomas (RCCs). It showed complete ablation in a single session without evidence of tumor recurrence at a mean of 10.8 months (10). Similar results have also recently been reported by other authors (11). Radiofrequency ablation (RFA) also has been reported to be a promising treatment for renal AML, included in a case report of computer tomography (CT)-guided RFA of a sporadic AML in a patient with a solitary kidney (12) as well as in a retrospective study that treated five selective patients and three post-SAE patients with RFA (13). Lately, the outcomes for a group of 15 patients with AML treated with RFA were reported (14). To our knowledge, MWA has several theoretical advantages over RFA in that it requires less dependence on the electrical conductivity of tissues and has fewer energy delivery limitations (15). However, there has been no report on MWA for renal AML. The purpose of the present study was to evaluate the efficacy and safety of US-guided percutaneous MWA in the treatment of sporadic renal AML.
Material and Methods
Patients
All treatments were performed at our institution with approval from the institutional ethics committee. Written informed consent was obtained from all patients who enrolled in this study. Fourteen patients with sporadic renal AML were treated with MWA from May 2006 to May 2011 and were then followed up continuously until December 2011. Five men and nine women (mean age, 49.2 ± 14 years; range, 30–86 years) were enrolled in this study group. Among the 14 patients, three patients had two lesions each, whereas one patient had three lesions. The long diameter of the lesions ranged from 0.8 to 6.1 cm (mean, 3.4 ± 1.7 cm), and the short diameter ranged from 0.6 to 4.5 cm (mean, 2.8 ± 1.3 cm) (Figs. 1 and 2). The patient information and tumor size are shown in Tables 1 and 2, respectively. Nine patients were found to have slight flank pain but no hematuria, and five were detected with no incidental symptoms in the health examination. Histologic diagnosis of all patients was confirmed by US-guided biopsy and the specimens were assessed independently by two pathologists without prior knowledge of the cases.
A hyperechoic lesion with well-defined borders was found in the lower pole of the left kidney. The lesion was demonstrated to be heterogeneous, hyper-enhancing under CEUS, and its dimensions were 4.8 × 4.1 cm. The baselines of the patients and tumors. The serial numbers of four lesions, which were considered to be incompletely ablated. A, anterior; L, lateral; P, posterior. Parameters of the tumors treated with MWA. The serial numbers of the four lesions that were considered to be incompletely ablated.
Equipment
A KY2000 MW ablation system (Kangyou Medical Instruments, Nanjing, China) consisted of two MW generators, two flexible coaxial cables, and two cooled-shaft antennae. The generator was capable of producing 1–100 W of power at 2450 MHz, which could drive up to one antenna. The cooled-shaft antenna had a 15-gauge shaft coated with polytetrafluoroethylene to prevent adhesion, which could be easily observed on US. Inside the antenna shaft, there were dual channels through which distilled water was circulated by a peristaltic pump, continuously cooling the shaft to prevent shaft overheating. The MW machine was also equipped with a thermal monitoring system that could measure temperature in real time during ablation.
Contrast-enhanced ultrasound (CEUS), contrast-enhanced CT, and/or magnetic resonance imaging (MRI) were employed to evaluate ablation efficacy and for a follow-up study. US and CEUS were performed using Sequoia US system (Acuson, Mountain View, CA, USA) with a 3.5–5.0 MHz linear multifrequency transducer. The US contrast agent was Sonovue (Bracco Company, Milan, Italy). All CT studies were carried out with the same multidetector row CT (Lightspeed 16, GE Healthcare, Milwaukee, WI, USA) and contrast medium (iopromide, Ultravist 300, Bayer Schering Pharma, Berlin, Germany). All MR studies were carried out with the same 1.5-T unit (Signa Echo-Speed, GE Healthcare, Milwaukee, WI, USA) and contrast medium (Magnevist, Schering; 0.1 mmol/kg body weight).
Techniques
Fourteen patients were treated according to the established protocol. The ablation zone aimed to cover or be smaller than the lesions because the renal AML was a type of benign tumor. The treatment protocol was designed according to the ablation range and the lesion location. In general, for lesions <1.7 cm in diameter, a single antenna was enough; for lesions in the range of 1.7–3.0 cm, multiple antennae were required. As for lesions >3.0 cm, antennae were firstly inserted into the deeper region and then were withdrawn gradually if the real-time ultrasonographic monitoring of hyperechogenicity covered the deeper region on US after a series of microwave emissions. Microwave emission was stopped when the hyperechogenicity covered the lesion along the axis of the antennae (Fig. 3). A thermal monitoring system attached to the MW unit was used during ablation. One or two 21 G MW thermal monitoring needles were inserted into the margin of the targeted tumor under US guidance. Heating of tissue at 50–55℃ markedly shortened the period needed to irreversibly damage cells in 4–6 min (16). According to our previous studies (17,18), temperatures near important structures, such as the colon or the “pelvis renalis”, were kept at 50–54℃ for no more than 3 min, with intermittent emission of MW.
Two 15-gauge cooled-shaft antennae were inserted into the lesion with a 1.4 cm space.
Local anesthesia with 1% lidocaine (Shuanghe; Beijing Pharmaceuticals, Beijing, China) was administered before US-guided biopsy, and then MW antennae were inserted via the same skin incision by US guidance. A general anesthetic (Propofol, 2.0 mg/kg, AstraZeneca, S.P.A., Milan, Italy) was conducted after proper placement of the antennae, and MW was then emitted. During ablation, the region of ablation was monitored by US. The treatment session was finished if the hyperechogenicity on grayscale US covered the entire target region. Ablation was performed before withdrawing the antenna to avoid bleeding. After MWA, intravenously administered antibiotics (ofloxacin, Sihuan; Sihuan Pharmaceuticals, Beijing, China) were routinely taken for 3 days or longer when there was a suspected infection.
Follow-up
To evaluate the lesion response to MWA (technique effectiveness), CEUS was performed to detect any residual viable tissues within 3 days after the treatment. The complete ablation of the lesion was considered to be achieved if the scans revealed the non-enhancing area just covered the lesion borders. The incomplete ablation was defined as an irregular hyper-enhancing area in the primary lesion. If the area of incomplete ablation was larger than one-quarter of the area of the primary lesion, another session was performed at 3–5-day intervals. If the area of incomplete ablation was smaller than that, the treatment was also considered to have achieved the expected efficiency. CEUS and contrast-enhanced CT or MRI were repeated at 1-month and 3-month intervals within 1 year and then at 6-month intervals after MW ablation.
Statistical analysis
The data were analyzed using SPSS (Statistical Program for Social Sciences, SPSS Inc., Chicago, IL, USA) for Windows (Version16.0). Patients’ ages and lesions size were expressed as means ± SDs, and the time of follow-up was expressed as median.
Results
Outcomes of MWA
Twenty-one sessions were performed on 19 lesions. Seventeen lesions achieved complete ablation that was monitored by US after one session of MWA, and two lesions (2/19, 10.5%) received a second session. Among all 19 lesions, 15 (15/19, 78.9%) achieved complete ablation confirmed by postoperative CEUS, and four were considered incompletely ablated (Fig. 4). The incompletely ablated areas were in the range of 0.5–1.9 cm (mean, 1.1 ± 0.6 cm) along the long diameter and 0.3–1.1 cm (mean, 0.6 ± 0.3 cm) along the short diameter. The follow-up period was 6–36 months (median, 10 months). No AML recurrence was observed during the follow-up, and no change was found for the volume of four incompletely ablated lesions. No AML-related symptoms were detected in any of the patients.
The greater part of the lesion was showed to be non-enhancing under the CEUS, and its dimensions were 5.3 × 4.1 cm.
Complications
A fistula of the descending colon occurred in one patient (1/14, 7.1%) whose occult blood test result was positive 2 days later. After 26 days, there was a subcutaneous lump (about 12 × 8 cm) in the left lateral abdominal wall that showed tenderness and a higher skin temperature. Intermittent fever appeared, and the highest recorded temperature was 38.8℃. After consultation, the patient was transferred to surgery and was debrided after a laparotomy. With complete drainage and antibiotic treatment for 1 month, the patient recovered with no permanent sequelae.
Local infection around the ablation zone was found in another patient (1/14, 7.1%) who suffered from persistent fever in the range of 38.6–39.7℃ 23 days later, and showed a swelling in right lateral abdominal wall. The occult blood test was also positive. After antibiotic treatment, the patient was treated with catheter drainage. Escherichia coli was detected upon draining liquid with a bacterial culture. Nineteen days later, the local infection was controlled, the catheter was removed and the patient recovered completely.
Patients neither had hematurias nor abnormalities in their routine urine tests during the periods of hospitalization and follow-up. The renal function of all patients was stable. Minor complications were found in most patients. Mild to moderate pain, according to the reporting criteria for image-guided tumor ablation (9), appeared in 11 patients (11/14, 78.6%), but no drug intervention was required. Fevers of 37.2–39.7℃ occurred on the day of MWA and lasted for 3 days in 11 patients (78.6%). The patients were encouraged to drink plenty of water. Slight subcapsular bleeding was observed in one patient (1/14, 7.1%) by US. No patient suffered from skin burns.
Discussion
Although renal AMLs are benign neoplasms, they attract disproportionate attention because of their characteristic radiologic appearance, occasional suspicion of malignancy, and potential association with severe complications (5,19). Renal AMLs tend to bleed and might cause a life-threatening retroperitoneal hemorrhage (2). The efficacy of treating patients with symptomatic renal AML was unambiguous, but there is still debate regarding the size criteria. Symptoms seldomly occur for tumors <4 cm in diameter, whereas for AMLs of 4 cm or larger, 80–90% are symptomatic and 50–60% tend to bleed spontaneously (20,21). Seyam’s study of 60 patients showed that renal AML had a slow growth rate; he also indicated a recent change, noting that there was a tendency to find smaller tumors in asymptomatic patients and that there had been changes in the use of conservative and interventional treatments (19). There was a mean growth rate of 0.088 cm/year in the patients with active surveillance (22), but an uncommon subtype, epithelioid AML, was potentially malignant and may behave more aggressive in terms of biology (5). Therefore, although only part of the lesions were >4.0 cm, the fear of growth and malignant change motivated patients to make a decision to engage in prophylactic treatment. For the same reasons, 15 renal AML patients who had lesions of a size (range) of 2.6 cm (1.0–3.7 cm) were also treated by RFA (14).
Selective angioembolization and NSS were the common treatment methods for AML, which can preserve normal renal tissue. In a larger cohort of 58 patients, NSS was successfully performed in all patients, with 12% of the overall complication rate and 3.4% of the local recurrence rate (7). Although selective angioembolization has also been used in the treatment for AML, the outcomes after embolization required critical review because re-embolization or subsequent surgical intervention had frequently been required in patients with recurrent bleeding, persistent symptoms, or lack of regression of the lesion (23). MWA was an additional ablation technology, which may be applied for the same indications as RF ablation but offers several advantages in energy delivery. Most importantly, microwave propagation was not limited by charred tissue, so intratumoral temperatures could be elevated consistently to a very high level (>150℃) without impairing energy deposition (24,25). Thus, the high temperature was more likely to overcome vascular-mediated cooling and create larger and more lethal ablation zones in a shorter treatment time (26,27). The potential benefits of MWA included minimal invasiveness, a high percentage of complete tumor necrosis, easy treatment for multiple lesions, lower costs than surgical resection, and improving quality of life (28).
In contrast to how we treat malignant tumors, we thought that the ablation zone extending 0.5–1 cm beyond the lesion was not suitable for renal AML. In our study, the complete ablation of the lesion was considered to be achieved if CEUS revealed an absence of enhancement in the lesion. If the area of incomplete ablation was too small, the treatment was also considered to achieve expectant efficiency. Only when the area of incomplete ablation was larger than one-quarter of the area of the primary lesion, another session was performed after 3–5 days. In our study, 15 (15/19, 78.9%) lesions were completely ablated after one session with one or two antennae; lesions two achieved complete ablation after a second session, and a small area of four lesions remained incompletely ablated.
In light of the nature of benign renal AML, the treatment plan should balance the benefits and complications. In this study, the complications and side-effects of MWA were analyzed. The major complication was a descending colon fistula, which occurred in one patient. To explain this case, first, a descending colon fistula in one patient was associated with the lesion location, which was in the anterior of the kidney and close to the colon (Fig. 5). Second, there was a large amount of fat in the AML that could easily reach a high temperature. The heat could not disperse easily in the fatty renal capsule or the narrow retroperitoneal space. Third, the descending colon was fixed in a narrow retroperitoneal space, so it could not avoid heat irritation through enterokinesia. Last, but not least, the permeability of the colon wall and the bacteria in the colon exudation increased after applying the heat irritation. Therefore, operators should be aware of intestinal tract injuries if lesions are close to the colon.
In the MRI, the lesion was closed to the descending colon.
To avoid major complication, a 3D navigation system and artificial ascites might be useful for keeping a safe distance from the colon wall. In addition, a thermal monitoring system might show the real-time core temperature of the ablation zone and around the colon wall, which could be helpful to regulate the output power and ablation time. Moreover, for the patients with renal AML adjacent to colon wall, it was necessary to perform a bowel preparation before MWA and to take a prolonged fast. Laparoscopic or CT-guided thermal ablation turned out to be better than ultrasound because it does not disturb the gas inside the colon. The reasons for the development of a local infection in the patient might be similar to those mentioned above.
In conclusion, MWA can provide an effective and minimally invasive renal-preserving treatment for AML with acceptable and treatable complications. Further confirmation and a long-term follow-up period are needed for further study. Additional randomized controlled studies are needed to ascertain whether MWA is a safer and more effective therapy for renal AML compared to other methods.
Footnotes
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.