A Child with Adrenocortical Carcinoma Who Underwent Percutaneous Ethanol Injection Therapy for Liver Metastasis
By Fujio Hara, Teruaki Kishikawa, Hirokazu Tomishige, Osamu Nishikawa, Yoshihisa Nishida, and Mutsumi Kongo Aichi, Japan
The authors encountered a 2-year-old-girl with adrenocorti- cal carcinoma who underwent percutaneous ethanol injec- tion therapy (PEIT) for liver metastasis. The patient had functional adrenocortical carcinoma diagnosed and under- went excision of the tumor in the right adrenal gland. Be- cause liver metastasis was detected 11 months after surgery, the patient underwent PEIT under general anesthesia. After the treatment, the size of the metastatic tumor was reduced
with calcification and then disappeared. The patient was in a good condition 3 years, 3 months after the occurrence of liver metastasis.
J Pediatr Surg 38:1237-1240. @ 2003 Elsevier Inc. All rights reserved.
INDEX WORDS: Adrenocortical carcinoma, percutaneous ethanol injection therapy, adrenogenital syndrome.
S URGERY IS THE most effective treatment for ad- renocortical carcinoma, and the prognosis is poor in patients in whom surgery cannot be performed or in whom metastasis is detected.1,2 We performed percuta- neous ethanol injection therapy (PEIT), in a girl with adrenocortical carcinoma accompanied by adrenogenital syndrome who had liver metastasis after surgery and obtained good results.
CASE REPORT
A 2-year-old girl was admitted to our hospital for detailed exami- nation of pubis and clitoral enlargement, which had been observed since the patient was 1 year and 6 months old. Her height was 88.9 cm (+1.9 SD), and her body weight was 12.6 kg (+1.0 SD), showing excess growth. Acne on the face and dark vellus hair around the mouth were observed. The patient had mammae at Tanner 1 stage and pubis at Tanner 2 stage, showing sexual precocity, and also had clitoral enlargement. At the same time, a fist-sized, solid, smooth-surfaced and immobile tumor was detected in the right upper abdomen by palpation.
Endocrinologic examination showed that the blood testosterone and estradiol levels were 379 ng/dL (normal range, 10 to 60 ng/dL) and 245 pg/mL (5 to 60 pg/mL), respectively, and the urine 17-KS level was 310.6 mg/d (2.4 to 11.0 mg/d), which were very high. The blood cortisol level was within the normal range. The age of the carpal bones seen by plain radiography was 5 to 6 years.
A round tumor of about 8 cm in diameter with a relatively clear boundary was detected in the right adrenal gland by abdominal com- puted tomography (CT) (Fig 1). The internal structure was almost homogeneous, but low-density areas were observed. The liver and right kidney were compressed by the tumor, but no infiltration was observed.
According to these findings, a tumor in the right adrenal gland accompanied by adrenogenital syndrome was diagnosed, and the pa- tient underwent surgery. The tumor was covered with a relatively thick capsule and had a clear boundary without infiltration. No swelling of the lymph nodes around the tumor was observed. The excised tumor measured 10 cm × 7.6 cm × 6 cm, with a weight of 275 g. A cross section of the excised tumor was homogeneously red-yellow, and hemorrhagic lesions and microcysts were partially observed (Fig 2).
Pathohistologically, a dense proliferation of cells with light cell bodies, nuclei of different sizes, and atypical nuclei were observed (Fig
3A), and necrosis and infiltration of blood vessels within the capsule were partially observed. Vimentin staining was negative. From these findings, adrenocortical carcinoma was diagnosed.
Four days after surgery, the blood testosterone level was 5.1 ng/dL, the blood estradiol level was 20 pg/mL, and the urine 17-KS level was 0.72 mg/d, which were within normal ranges. Therefore, chemotherapy was not performed, and the patient was discharged 14 days after surgery. Follow-up observation was performed in the outpatient clinic. Eleven months after surgery, 2 metastatic lesions of about 15 mm in diameter were detected at segment 6 and 7 in the liver by CT (Fig 4A and B). The blood testosterone, blood estradiol, and urine 17-KS levels were within normal ranges. Because a large part of the normal liver had to be excised together with the 2 lesions and because treatment would be difficult if metastatic lesions occurred after excision, we considered PEIT or systemic chemotherapy rather than surgery. PEIT was selected because chemotherapy is not so effective for adrenocortical carcinoma.
Under general anesthesia and under ultrasonographic observation, a needle biopsy was performed before the ethanol injection. After the lesion was scanned with a puncture guide transducer, a 21-gauge needle was introduced into the tumor and the absolute ethanol was injected slowly. The biopsy performed before PEIT showed that the metastatic lesions consisted of large swollen cells with nuclei of different sizes and atypical nuclei, identical with the primary tumor (Fig 3B). Over a period of 2 months, PEIT was performed 3 times. The volume of ethanol injected was 1.4 mL in the first PEIT and 3 to 4 mL in the second and third PEIT. After PEIT, mild transient liver function abnormalities were observed, but no severe side effects or complica- tions occurred.
Computed tomography scan 1 month after the first PEIT showed that the tumor at segment 7 was enhanced heterogeneously, and there were slight low-density areas around the tumors. After the third PEIT, the tumors and their surroundings showed large low density areas. The
From the Department of Pediatric Surgery, Fujita Health University School of Medicine, Aichi, Japan.
Address reprint requests to Fujio Hara, Department of Pediatric Surgery, Fujita Health University School of Medicine, 1-98 Dengaku- gakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
@ 2003 Elsevier Inc. All rights reserved. 0022-3468/03/3808-0022$30.00/0 doi:10.1016/S0022-3468(03)00276-8
tumor started to calcify and decrease in size about 8 months after PEIT. One year and 10 months after PEIT, a low-density area with calcifi- cation shown by CT remained (Fig 4C), but the tumor was not enhanced. The tumor at segment 6 in the liver was not detected (Fig 4D). Therefore, we considered that the viable tumor cells had disap- peared. Three years and 3 months after the detection of the metastatic lesions, the blood testosterone, estradiol, and urine 17-KS levels were within normal ranges, and the patient was in good condition.
DISCUSSION
PEIT is an established treatment for hepatocellular carcinoma in adult patients and is performed under ul- trasonography and local anesthesia. It is performed usu- ally on lesions smaller than 3 cm in diameter and on 3 or fewer metastatic lesions.3 However, PEIT has been per- formed recently on lesions larger than 3 cm in diameter by the multiple-needle insertion method,4 and is widely used for the treatment of metastatic liver cancer as well as primary cancer.5 PEIT is performed routinely twice a week with 2- 8-mL ethanol injections. The total amount of ethanol required for complete destruction of a tumor lesion is about 4 mL for a lesion of 1 cm in diameter, 14 mL for a lesion of 2 cm in diameter, and 33 mL for a lesion of 3 cm in diameter. PEIT cannot be performed on patients in whom ascites can not be controlled or in whom marked bleeding tendency is observed, but it is possible for tumor lesions located in any part of the liver as long as they are imaged by ultrasonography.6 Com- mon complications of PEIT are transient pain, fever, and a feeling of alcohol intoxication. The changes in liver function are milder after PEIT than in surgical resection or transcatheter arterial embolization. Serious complica- tions reported were intraperitoneal hemorrhage, pleural effusion, and hemothorax, all of which were treated conservatively.6 To our knowledge, there has been only one report of PEIT performed in a child.7 The child was a 4-year-old girl with hepatocellular carcinoma who
underwent surgery for biliary atresia. As PEIT is per- formed in children under general anesthesia, the time and intervals of PEIT are restricted, and the number of pediatric patients with disease conditions requiring PEIT is small. During the first PEIT in our patient, the ethanol injection was stopped just as leakage of the ethanol from the tumor was detected by ultrasonography. After that, side effects, complications, and the effects of PEIT on the tumor were observed. No severe side effects or complications occurred. Because the tumor became en- hanced heterogeneously by CT 1 month after PEIT, although the size of the tumors did not change, we judged PEIT to be effective. Therefore, in the second and third PEIT, larger amounts of ethanol were injected at an interval of one week. Although the ethanol leaked around the tumor, no side effects or complications, except for mild liver function abnormalities, were observed. Thus, PEIT was performed safely in a child without serious side effects.
Adrenocortical carcinoma is relatively rare in children and often is accompanied by some endocrine activity.8,9 Surgery is the most effective treatment for adrenocortical carcinoma, and the prognosis is relatively good in pa- tients in whom the tumor is excised completely but poor in patients with incomplete excision or when surgery could not be performed.1 Distant metastases are observed mainly in the lung and liver. For patients with metastatic lesions, the survival rate is high if excision of both primary and metastatic lesions is possible.1º For patients with a poor prognosis, when not only chemotherapy with a combination of drugs consisting of 5-fluorouracil, doxorubicin, and cisplatin,11 or consisting of cisplatin and etoposide,12 but also chemotherapy with mitotane has been performed, the effects of chemotherapy are
A
B
A
B
y
C
D
neither decisive nor consistent. However, PEIT is effec- tive in treating liver metastases, which are not expected to be improved by the administration of carcinostatics
from adrenocortical carcinoma. Although PEIT requires general anesthesia for pediatric patients, this method is considered to be safe, useful, and without side effects.
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