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1
Department of Diagnostic Radiology, Asan Medical Center, University of Ulsan
College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736,
Korea.
2
Department of Endocrinology, Asan Medical Center, University of Ulsan College
of Medicine, Seoul 138-736, Korea.
Received February 9, 1999;
accepted after revision June 29, 1999.
Address correspondence to H. K. Lee.
Abstract
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SUBJECTS AND METHODS. We examined 22 patients with benign thyroid cysts (13 complex cysts and nine pure cysts) confirmed by fine-needle aspiration biopsy. Sonographically guided aspiration of the cystic fluid was followed by instillation of absolute ethanol (99.9%) into the cystic cavity: the injected volume of ethanol was 40-100% of the volume of fluid aspirated. The procedure was performed every 1 or 3 months for one or two sessions (mean, 1.2 sessions). Follow-up sonography was performed 1-10 months after the final session, and we observed patients after ethanol sclerotherapy for complications.
RESULTS. The initial volume of the cysts ranged from 3.5 to 42 ml. In 21 patients, the volume of the cyst decreased or the cyst was obliterated. The volume of the cyst was reduced by 50-99% in 13 patients and by 1-49% in six patients, and the cyst was obliterated in two patients. In one patient, the volume of the cyst increased. The volume of ethanol instilled was significantly correlated with the volume reduction rate of the cyst. There was a difference in the volume reduction rate between patients in whom 10 ml or more of initial volume was used and those in whom less than 10 ml of initial volume was used; that is, the volume reduction rate of the group with the initial cyst volume of more than 10 ml was higher than that of the other group. Important long-standing and severe complications were not observed.
CONCLUSION. Sonographically guided ethanol sclerotherapy is a safe and effective tool for the therapy of benign thyroid cysts.
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Sonographically guided percutaneous ethanol injection was first used for treatment of renal cysts and has been reportedly used for the treatment of autonomous thyroid adenoma with an efficacy rate of approximately 80% [12, 13, 14, 15]. Several researchers have reported the efficacy and safety of ethanol sclerotherapy for thyroid cystic nodules [5, 8,16, 17]. Hence, we intended to determine the efficacy and safety of sonographically guided ethanol sclerotherapy (hereinafter referred to as "sclerotherapy") for benign thyroid cysts.
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Most patients (n = 19) were concerned about the cosmetic implications of the nodules, and a few patients complained of local discomfort (n = 1) and dysphagia (n = 1) and expressed fear about malignancy (n = 1).
For sonography, an HDI 3000 scanner (Advanced Technology Laboratories,
Bothell, WA) was used with a 5-10-MHz linear probe. The volume of a cyst,
except a complex cyst, was determined using the following formula: length
x width x height x 
/6. For a complex cyst, volume was
calculated as the volume of the cystic component other than solid areas.
Under sonographic guidance, a 20- to 22-gauge needle was inserted to aspirate cystic fluid as completely as possible without local anesthesia and then ethanol was slowly (approximately 2-5 ml/min) instilled into the cavity to a volume of 40-100% of the volume of aspirated fluid. The injection of ethanol was stopped if ethanol leaked out of the nodule or the patient complained of pain.
Four patients underwent sclerotherapy twice and the remaining 18 patients underwent the procedure once. Follow-up sonography was performed 1-10 months (mean, 3.5 months) after the final session and the side effects of ethanol sclerotherapy were evaluated by recording the symptoms of patients. The effectiveness of sclerotherapy was compared between two groups: in one group, 10 ml or more of baseline volume was injected; in the other group, less than 10 ml. In addition, the correlation between the volume of ethanol injected and the effect of sclerotherapy was determined. The effect of the therapy was presented as the volume reduction rate (volume reduction rate [%] = volume decrease [initial volume — final volume after treatment] / initial volume x 100%), and each case was classified into one of the following four groups: completely ablated cysts, cysts with a 50-99% reduction in volume, cysts with a 0-49% reduction in volume, and cysts with an increase in volume.
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The correlation between the volume of ethanol instilled and the volume reduction rate of cysts was confirmed: the higher the volume of ethanol instilled, the higher the rate of the volume reduction (r = 0.77, p < 0.01; Pearson's correlation analysis) (Table 2)x. However, no significant difference in the rate of volume reduction for either pure or complex cyst was seen (p > 0.005; two sample t test).
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There was a difference in volume reduction rate between two groups—those in whom 10 ml or more of initial volume was injected and those in whom less than 10 ml of initial volume was injected; that is, the rate of volume reduction was higher for the group with the initial cyst volume of more than 10 ml when compared with the other group (p < 0.005; two sample t test).
Side effects associated with sclerotherapy were reported in two patients, both of whom complained of local pain at the injection site caused by leakage of a small amount of ethanol into the subcutaneous tissue. Pain was transient in both patients, and no severe complications were seen.
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Thyroid cysts rarely accompany malignant neoplasia. These cysts present as thyroid carcinoma in an average of 5% of patients, a lower probability than that of solid nodules [8]. Pure cysts are associated with a lower probability of malignancy than mixed cysts [5]. Malignant thyroid cysts confirmed by fine-needle aspiration biopsy usually require surgical treatment. However, for benign thyroid cysts, percutaneous tetracycline instillation, ethanol sclerotherapy, or thyroid hormone suppression therapy can be performed. Among these treatments, percutaneous aspiration has shown a high recurrence rate of up to 58% depending on the size of the cyst. Hence, for the treatment of recurrent cases, methods such as thyroid hormone suppression therapy and sclerosant instillation (sodium tetradecyl sulfate, hydroxy-polya-ethoxy-dodecan, tetracycline, or ethanol) were performed [18, 19]. Thyroid hormone suppression therapy was found to have no effect, whereas tetracycline instillation has been shown to be relatively effective. However, in a prospective study, researchers reported that tetracycline did not offer any advantage over isotonic saline in the treatment of thyroid cysts [20].
Ethanol, which is distributed in tissue by a diffusion mechanism, induces cellular dehydration and protein denaturation, which is followed by coagulation necrosis and reactive fibrosis [21].
Yasuda et al. [17] reported that the volume of the cyst decreased by more than 50% with ethanol sclerotherapy in 73% of patients treated for recurrent thyroid cysts after fine-needle aspiration. In our study, 68% of the patients with cystic nodules showed a decrease in volume of 50% or greater. Monzani et al. [16] also reported in a study in which they performed ethanol sclerotherapy and 12-month follow-up that cysts had relapsed in six of 20 patients, five of whom had a recurrence by the first month of follow-up, implying that most recurrence would occur within 1 month after treatment.
According to the report of Yasuda et al. [17], although no correlation between the volume of ethanol instilled and the volume reduction rate was seen, the recurrence rate after ethanol sclerotherapy was lower in the patient group in which the volume of aspirated fluid was less than 10 ml than in the other group. The results of our study, however, differ from those of Yasuda et al. We found the rate of volume reduction was greater in the group in which the volume of aspirated fluid was 10 ml or more compared with that of the other group in which the aspirated volume was less than 10 ml; in addition, we found that the more ethanol instilled, the greater the volume reduction rate of cysts. The reason for this difference is thought to be related to the fact that we used larger volumes of ethanol for our procedures than did Yasuda et al.
Although in recent studies some investigators reporting the effects of ethanol sclerotherapy have chosen to instill ethanol by the volume of one tenth to one third of the aspirated volume, we injected a higher volume of ethanol (approximately 40-100% of the aspirated fluid). According to our findings, the volume reduction rate increased, and side effects were not increased with more ethanol instilled. Therefore, we recommend that more ethanol be instilled to get an improved ablation effect in treatment for thyroid cyst. However, the chemical components or the viscosity of fluid are thought to inhibit diffusion of ethanol and, therefore, decrease the ablation effect.
Although investigators have reported there is a differences in the effects of sclerotherapy for thyroid nodules other than thyroid cysts, the effects of sclerotherapy for thyroid nodules differ little from those for thyroid cysts.
The frequency of complications after ethanol sclerotherapy is lower in thyroid cysts than thyroid nodules [12, 13, 14, 15, 21]. Complications of ethanol sclerotherapy, such as local pain at the injection site, transient hyperthyroidism, transient hoarseness, hematoma, and dyspnea, have been reported by several investigators [22, 23, 24]. Local pain at the injection site, the most common complication reported by all the investigators, occurs as a result of the leakage of ethanol into the subcutaneous tissue. Transitory hyperthyroidism has been reported by Antonelli et al. [8] and Kobayashi et al. [24]. In our study only two patients (9%) experienced transient local pain due to the leakage of a small amount of alcohol. However, because a thyroid function test was not performed before and after the sclerotherapy, thyroid function could not be evaluated.
In our series, several points can be mentioned as limitations. First, follow-up sonography was not performed at a regular interval. Second, although the volume reduction rate was found to increase with an increasing amount of ethanol, we could not determine the effective amount of ethanol relative to the volume of a cyst or the amount of aspirated fluid. The relationship between the chemical components and the viscosity of cystic fluid and the ablation effect of ethanol will need to be investigated to increase efficacy of ethanol sclerotherapy. Sometimes it is difficult to aspirate cystic fluid because of its higher viscosity; when this occurs, repeated instillation of ethanol is recommended. In addition, as we mentioned earlier, because the characteristic of cystic fluid might affect the treatment positively, we think more detailed studies regarding this point are necessary.
In conclusion, sonographically guided ethanol sclerotherapy is a safe and effective treatment for benign thyroid cysts.
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