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CT-Guided Percutaneous Chemical Ablation of Adrenal Neoplasms

¹ All authors: Department of Radiology, Chinese PLA General Hospital, Fuxing Rd. 28, Beijing, 100853, China.

Received February 28, 2007; accepted after revision August 21, 2007.

 
Address correspondence to Y. Y. Xiao (xiaoyueyong{at}vip.sina.com).

Abstract

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OBJECTIVE. The objective of our study was to evaluate the feasibility and effectiveness of percutaneous chemical ablation of primary and metastatic adrenal neoplasms under CT guidance.

MATERIALS AND METHODS. Thirty-seven patients with 46 adrenal tumors underwent CT-guided percutaneous chemical ablation. The average (± SD) tumor diameter was 4.2 ± 2.0 cm. Acetic acid was injected in lesions with a diameter of more than 3 cm, and ethanol was injected in lesions with a diameter of less than 3 cm. Eleven adrenal lesions were nonfunctional adenomas, six lesions were corticosteroid adenomas (bilateral lesions in one patient), nine lesions were aldosteronomas (bilateral lesions in two patients), and 20 were metastases (bilateral metastases in six patients).

RESULTS. Tumor volume decreased gradually during the first 2 years after the procedure. For primary tumors, a complete response (CR) rate of 92.3% (24/26) and a partial response (PR) rate of 7.7% (2/26) were obtained, but for metastasis, a CR rate of 30% (6/20) and PR rate of 70% (14/20) were obtained 24 months after therapy. The level of corticosteroid in five patients (six tumors) with Cushing's syndrome was in the normal range 3 months after the procedure. Seven patients (nine tumors) with Conn's syndrome began receiving oral antihypertensive medications during the first month after the procedure to maintain normal blood pressure and the dose was gradually decreased after 1 month. No severe complications were encountered.

CONCLUSION. CT-guided percutaneous chemical ablation of adrenal tumors is an effective, minimally invasive, and easily performed procedure.

Keywords: ablation • acetic acid • adrenal gland neoplasms • Conn's syndrome • CT guidance • Cushing's syndrome • ethanol

Introduction

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Primary adrenal neoplasms include nonfunctioning adenomas, adrenal cortical carcinomas, cortisol-producing adenomas, pheochromocytomas, and aldosteronomas. The traditional treatment for primary adrenal neoplasms has been open surgical resection and laparoscopic resection [1-3]. Surgical resection for isolated adrenal metastasis has been advocated by some authors, although this treatment remains controversial [4-7]. Less invasive techniques for the treatment of adrenal neoplasms have been described [4, 5]. These include radiofrequency ablation, selective arterial embolization, and injection of alcohol or acetic acid (chemical ablation). Although chemical ablation has been used to treat neoplasms of the liver, bone, kidney, lung, and other organs [8-11], to our knowledge, only a few reports on a limited number of patients treated with chemical ablation for adrenal neoplasm have been published [6, 7, 12]. The purpose of our study was to evaluate the feasibility of chemical ablation for adrenal neoplasms in a cohort of patients treated at our institution.

Materials and Methods

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Patients
We performed a retrospective study of 37 consecutive patients who were referred to our institution from July 2001 to December 2005 for CT-guided percutaneous chemical ablation of solid adrenal masses. This study was approved by our hospital review board. Referred patients were not surgical candidates because of comorbid conditions, disease at other sites, or unwillingness to undergo surgery. There were 28 men and nine women. The average patient age was 48.3 years (range, 32-69 years).

Acetic acid has the ability to penetrate tumor septa and is known to diffuse better throughout a lesion than ethanol; in addition, a smaller volume of acetic acid is needed to chemically ablate a lesion. Therefore, acetic acid was injected in 29 lesions with a diameter of more than 3 cm for 23 patients and ethanol was injected in 17 lesions with a diameter of less than 3 cm for 14 patients. Nine patients had bilateral adrenal masses.

View larger version (153K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —41-year-old man with left adrenal metastasis. Transverse CT scan obtained with patient in prone position shows needle (arrow) in left adrenal mass (arrowheads).

View larger version (147K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —41-year-old man with left adrenal metastasis. Image obtained after second injection of acetic acid and iodized oil shows good permeation of compound (arrow).

View larger version (152K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C —41-year-old man with left adrenal metastasis. Six months after A and B, follow-up CT image shows dotlike lesion (arrowhead) remains and iodized oil is within diaphragm.

View larger version (145K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D —41-year-old man with left adrenal metastasis. One year after A and B, follow-up CT image shows lesion has fully resolved.

Procedure
The coagulation profile, including prothrombin time, bleeding time, and coagulation time, was checked in each patient, and plasma biochemical assay and plasma viruses, including hepatitis B surface antigen, hepatitis C surface antibody, HIV antibody, and syphilis antibody, were also checked. Patients were instructed to fast for 6 hours before the procedure. Diclofenac sodium (75 mg) was administered orally 30 minutes before treatment. For patients with functional aldosteronomas, a supplement of potassium chloride was given before treatment if the serum potassium level was less than 3 mmol/L to avert hypokalemia, which might occur during or after the procedure owing to excessive release of aldosterone. Spironolactone (30 mg, three times per day) was administered orally 24 hours before the treatment.

During the procedure, ECG, blood pressure, and peripheral blood oxygen saturation level were carefully monitored. Vital signs were also closely observed for the first 4 hours after the procedure beginning once the patients had returned to their ward. The range of hospital stay was 3-5 days. To evaluate the efficacy of treatment, follow-up biochemical studies and CT were performed every 3 months in each patient. If the patient experienced pain after the procedure, acetaminophen or meperidine hydrochloride (50 mg) was injected intramuscularly.

For the procedure, each patient was positioned prone and a local anesthetic of 1% lidocaine was injected at the site of skin puncture. With CT guidance, a 22-gauge Chiba needle (coaxial needle) was inserted through the posterior paraspinal muscle into the center of the lesion. To avoid a needle path through the posterior pleura, the CT gantry was angled for guidance in four patients.

The injected volume, V, was determined on the basis of the following formula:

where R is the radius of the tumor. For small lesions (< 3 cm), alcohol was used for the ablation. For large tumors (> 3 cm), a 50% acetic acid solution (99.9% acetic acid added the half of iodized oil) was used. A single needle was used for small lesions. For large lesions, two or three needles were advanced into the tumor, and the needles were slowly backed out during injection. CT was performed after each one third of the calculated volume was injected. Injection was stopped if bulging of the tumor capsule was observed during the injection. We left the needle in the tumor for 10 minutes after ablation to avoid reflux along the needle track. The decision to administer a repeat injection was based on follow-up CT findings. Treatment was repeated an average of three times for small lesions and five times for large lesions.

Results

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CT Findings
A complete response (CR) was defined as the disappearance of all lesions. Partial response (PR) was defined as a reduction of at least 30% in tumor diameter [13]. Tumor volume decreased gradually during the first 2 years after procedure (Table 1). For primary tumors, a CR rate of 92.3% (24/26) and a PR rate of 7.7% (2/26) were obtained, but for metastasis, the CR rate was 30% (6/20) and the PR rate was 70% (14/20) 24 months after therapy. In the circumstance of a CR, either the lesion had fully disappeared (Fig. 1A, 1B, 1C, 1D) or the tumor was replaced by fatty tissue and residual fibrotic debris could be observed in some patients on contrast-enhanced CT (Fig. 2A, 2B, 2C, 2D). In some patients, the apparent tumor volume did not change but included large areas of hypoattenuation (necrosis) that showed no enhancement on contrast-enhanced CT and no changes in size on subsequent follow-up CT.

View larger version (160K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —Primary left adrenal adenoma in 39-year-old man. Transverse CT image obtained with patient in prone position shows fine needle (arrow) in left adrenal mass (arrowheads).

View larger version (132K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —Primary left adrenal adenoma in 39-year-old man. CT image obtained after first injection of alcohol reveals focal collection of alcohol in adrenal tumor (arrowhead).

View larger version (170K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —Primary left adrenal adenoma in 39-year-old man. CT image obtained after third ethanol injection shows distribution of alcohol in tumor (arrowheads) is more diffuse than in B.

View larger version (89K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —Primary left adrenal adenoma in 39-year-old man. Follow-up CT image obtained 1 year after A-C reveals that most of lesion (arrowheads) is replaced by fatty tissue.

Clinical Data
Each patient's baseline adrenal function was assessed before and after treatment. In the 11 patients with nonfunctional adenomas, normal glucocorticoid and mineralocorticoid functions were found before and after treatment; blood pressures were also normal before and after treatment.

In the seven patients with aldosteronomas (nine lesions), blood potassium, blood renin, and angiotensin II levels ascended after the first treatment but were in the normal range 1 week after the last treatment. Blood aldosterone levels began descending after the first treatment and returned to within the normal range 1 week after the last treatment (Table 2). Blood pressure lowered gradually, even the serous hormone levels were normal, and patients received oral antihypertensive medications for 1 month after the procedure to lower blood pressure to within the normal range; the dose was decreased gradually thereafter.

In the five patients with corticosteroid adenomas (six lesions), plasma cortisol levels decreased after the first treatment and reduced to within the normal range 1 week after the last treatment (Table 3). The results of an adrenocorticotropic hormone stimulation test and dexamethasone suppression test were normal 24 months after the treatment. Blood pressure lowered gradually, and the treatment was the same as that for patients with aldosteronomas.

In 14 patients with metastasis, test results showed normal adrenal function before and after treatment.

Complications
There were no major complications in any of the patients except pain during and after the procedure. Seventy percent of the patients had minimal pain during the procedure, and the pain palliated after 2-3 mL of 1% lidocaine was injected slowly into peritumor tissue. After the procedure, the pain subsided without medication in 5-6 hours. Eleven patients had severe pain during the procedure. Meperidine hydrochloride (50 mg) was injected intramuscularly in addition to 2-3 mL of 1% lidocaine injected locally. Five patients who still had acute pain after injection were treated with acetaminophen or meperidine hydrochloride (100 mg). No patient developed hypertension during or after the procedure. Neither hemor-rhage nor infection at the needle insertion site was observed in any patient.

Follow-Up
All the patients were followed up for the first 2 years after treatment. All patients were symptom-free at 1-year follow-up except two patients with aldosteronomas who still developed hypertension and required oral antihypertensive drugs (Tables 2 and 3). Follow-up CT images obtained 6, 12, and 24 months after the procedure showed complete cystic change with regression of tumor size in 23 patients with benign adrenal tumors (Table 1). One year after the procedure, the size of eight metastatic lesions injected with acetic acid had decreased in six of 14 patients, five lesions in three patients were controlled in size but the extraadrenal primary tumor had enlarged, and five patients with seven lesions died due to extraadrenal metastases.

Discussion

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CT-guided chemical ablation shows promise as a minimally invasive therapy for the treatment of adrenal neoplasms. Our preliminary results show that there is minimal morbidity associated with this procedure. Follow-up imaging and biochemical assay results indicate that chemical ablation can effectively destroy both native adrenal tissue and metastatic lesions of the adrenal gland. Although we studied different neoplasms in the adrenal gland, our findings are similar to the results described by Liang and colleagues [12] who treated primary adrenal tumors in three patients. They found that acetic acid injection had minimal morbidity and was a safe, effective, and minimally invasive therapy for the treatment of small functional adrenal cortical adenoma.

Our results suggest that small benign tumors (< 3 cm in diameter) can be treated completely with one to three percutaneous ethanol injections. For large lesions (> 3 cm in diameter), tumor size regressed gradually after acetic acid injection. For malignant lesions, acetic acid injection may control or delay the progression of the malignancy because they may be associated with a higher incidence of residual tumor and recurrence in adrenal or extraadrenal sites. For functional tumors, CT-guided chemical ablation can reduce the level of hormone to normal 3 months after the procedure. However, for functional aldosteronomas, blood pressure may not decrease obviously after the procedure because of arteriolar sclerosis caused by long-term hypertension.

Although our results indicate that chemical ablation is effective for local control of disease, proper selection of patients who are candidates for this procedure will be critical in the assessment of the overall role of adrenal chemical ablation. Our study results indicate that if bilateral large metastases (> 5 cm in diameter) occur in patients with or without extraadrenal primary tumors, chemical ablation is a poor alternative and thermal ablation, such as radiofrequency ablation, may be a good alternative. Because of concern for hypertensive crises [14], we did not include patients with functional pheochromocytomas in our study.

Ethanol and acetic acid are the most common chemical ablation agents, which accomplish tumor necrosis by degenerating cellular cytoplasm and completely denaturing cellular proteins, with irreversible vascular thrombosis of the small vessels supplying the tumor [11]. However, ethanol has difficulty penetrating tumor septa and diffusing fully within the tumor. Thus, ethanol is not suitable for the treatment of large tumors (> 3 cm in diameter). Acetic acid has been shown to be able to diffuse through tumor septa, and a smaller volume of this agent can achieve the same volume of cell killing as ethanol. Some authors have reported that acetic acid produced a three- to 10-fold greater area of necrosis than did an equal volume of ethanol in small hepatocellular carcinomas and that the histologic changes induced by the two agents were identical [15].

The intraprocedural visibility of injected ethanol under CT, which is seen as a region of hypoattenuation, is superior to that of acetic acid. The latter often needs to be mixed with a water-soluble contrast material to be seen on CT. Therefore, in lesions smaller than 3 cm, ethanol was used because it was thought that acetic acid would spread into the surrounding tissues and cause pain; for lesions greater than 3 cm, a mixture of acetic acid and iodized oil was used.

CT is the imaging technique that is preferred for the performance of adrenal chemical ablation because of its accurate localization. In addition, the fine needle (22-gauge) minimizes injury of tissues in the needle track.

Our study was limited because of its retrospective design and the varied types of tumors treated. In addition, fine-needle aspiration as a pathologic aid in diagnosis may not be the method that can distinguish between hyperplastic nodules and adenomas. Hyperplastic nodules in aldosteronism are often the same size as adenomas. The diagnoses were mainly based on clinical history and laboratory assessment. This may reduce the value of the study.

In summary, our preliminary results suggest that CT-guided percutaneous chemical ablation is feasible for local control of small adrenal neoplasms. It can be a good alternative treatment in patients with high surgical risk. However, the application of this technique to replace surgical adrenalectomy in all patients with small adrenal neoplasms requires additional investigations in large numbers of patients.

References

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