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RCR RADIOLOGY CASE REPORTS
Case Report
Adrenocortical carcinoma with multiple liver metastases controlled by bland transarterial embolization and surgery resulting in long-term survival*
Kiichi Watanabe, MDª,*, Yoshihisa Kodama, MD, PhDa, Yasuo Sakurai, MDª, Beni Yamaguchi, MDª, Koji Yamasaki, MDa,d, Atsushi Ishiguro, MD, PhDb, Yoshiyasu Ambo, MD, PhDc
ª Department of Radiology, Teine Keijinkai Hospital, 1-12-1-40 Maeda Teineku, Sapporo, 006-8555, JAPAN
b Medical Oncology, Teine Keijinkai Hospital, 1-12-1-40 Maeda Teineku, Sapporo, 006-8555, JAPAN ” Surgery, Teine Keijinkai Hospital, 1-12-1-40 Maeda Teineku, Sapporo, 006-8555, JAPAN
d Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Kita14 Nishi5 Kita-ku, Sapporo, 060-8648, JAPAN
ARTICLE INFO
Article history: Received 13 January 2022 Revised 18 January 2022 Accepted 19 January 2022
Keywords: Adrenocortical cancer Bland transarterial embolization Microspheres Liver metastases
ABSTRACT
Adrenocortical carcinoma (ACC) is a rare malignant tumor with a poor prognosis. Local re- currence or distant metastases occur in more than 50% of cases. Patients with metastases have limited treatment options, and <15% have a 5-year survival time. Herein, we describe a 44-year-old woman with ACC and who underwent retroperitoneal tumor resection. Multi- ple liver and lung metastases were found 1-year postresection. Mitotane therapy started as systemic treatment. Lung metastases were controlled but liver metastases were progressive. The liver metastases were treated by performing 2 resections and 6 bland transarterial em- bolization (bland TAE), and are presently controlled with only 2 liver metastases of <20 mm. The present case showed that bland TAE can achieve long-term prevention of the progres- sion of liver metastases of ACC. The ultraselective bland TAE for selective embolization sup- ported by the latest computed tomography analysis techniques during arteriography could minimize liver damage caused by embolization and allowed multiple treatments which pro- longed survival. We conclude that bland TAE can be effective for controlling liver metastases of ACC.
@ 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
* Patient Consent: Patient consent was obtained from the patient for publication of this case report.
* Corresponding author. E-mail address: kiichi686@gmail.com (K. Watanabe).
https://doi.org/10.1016/j.radcr.2022.01.052
Introduction
Adrenocortical carcinoma (ACC) is a rare malignant tumor with a poor prognosis [1]. Many ACC cases are diagnosed in the late stages with distant metastases. Complete surgi- cal resection is the only curative method for localized dis- ease. However, local recurrence or distant metastases occur in more than 50% of cases. Patients with metastases have limited treatment options, and < 15% have a 5-year survival time [2,3]. Mitotane is the only available drug specific for ACC, and treatment options are limited owing to their serious side effects and the very narrow range of treatment. Fassnacht et al. showed improvement of progression-free survival by etoposide-doxorubicin-cisplatin-mitotane (EDP-M) compared with streptozocin-mitotane in patients with stage III-IV dis- ease [4]. Thus, EDP-M has become the standard chemotherapy for ACC. However, the survival benefits of nonchemotherapy treatments remain lacking. Transcatheter arterial chemoem- bolization (TACE) and bland transarterial embolization with- out an anticancer agent (bland TAE) for liver metastasis are very effective treatment options with good results. Indeed, TACE and bland TAE have been widely used in the treatments of hepatocellular carcinoma (HCC) [5-8] and liver metastases from neuroendocrine tumor [9-12], colorectal cancer [13,11], and lung cancer [11]. However, there are still few reports of TACE or bland TAE for the treatment of ACC liver metasta- sis [14-16]. Herein, we reported an ACC patient who achieved a long-term survival of 8 years or more by a combination of repeated bland TAE, surgery and mitotane therapy. Addition- ally, some liver metastases showed a high rate of complete response to bland TAE alone.
Case report
A 44-year-old woman presented with abdominal distention as the chief complaint. There were no other specific com- plaints including appetite or weight loss. She had no medi- cal history without medications or family history. Abdominal contrast-enhanced computed tomography (CT) showed a 160 mm retroperitoneal tumor which deviated the caudal side of the left kidney without metastasis. Blood samples showed no hormonal abnormalities. Retroperitoneal tumor resection was performed. The pathological diagnosis was left ACC Stage II under the UIC/WHO classification stage (T2N0M0).
One year postoperation, multiple liver and lung metastases were found. Thus, mitotane therapy was started. 1year af- ter starting mitotane therapy, the lung metastases were con- trolled but the liver metastases progressed. Therefore, 2 cy- cles of EDP-M therapy were administered, but there was no treatment response. Liver metastases were distributed pre- dominantly in the posterior segment (60 mm and 50 mm in S7; 50 mm in S6; 25 mm in S5). The progression rate of the liver metastases was higher than that of the lung metastases, suggesting liver metastases as a prognostic factor. Posterior segmentectomy plus S5 partial hepatectomy were thereafter performed. 1 year after the hepatectomy, new multiple liver metastases were observed. The patient decided not to undergo
any surgical resection, thus other options were discussed. Liver metastases were enhanced strongly in the arterial dom- inant phase (Fig. 1A), suggesting that bland TAE or TACE may be effective.
In our country, there are still no anticancer agents arterially administered for ACC treatment. Therefore, bland TAE was se- lected as a treatment option. Bland TAE was repeated when necessary, adopting a usage policy when the maximum size of the liver metastases was >2 cm. For the embolic materials, 100-300um microspheres were used. Before the bland TAE, CT during arteriography was performed for feeding artery anal- ysis. Catheterization was performed as selective as possible by using selective microcatheter with 1.5F or 1.7F tip for ul- traselective bland TAE (Fig. 1B,C). Bland TAE was performed 6 times over a 3-year period. 8 liver metastases were treated, of which 5 lesions showed a complete response (Fig. 1D). 1 lesion on the hepatic surface of S4 was fed by some branches via the internal thoracic artery. As the parasitic artery could not be controlled by bland TAE alone, partial resection was added for this nodule. The other 2 lesions were <2 cm and are cur- rently under follow-up. During the course of the disease, the liver functional reserve has been maintained. As for the lung metastases, they showed a slow increase. The patient remains alive 8 years after the initial surgery. Clinical course was sum- marized in Fig. 2.
Discussion
ACC is a rare malignant tumor with a poor prognosis, partic- ularly in patients with metastatic disease [1-3]. The lung and liver are the 2 most common organs where distant metastases occur. In particular, liver metastases greatly affect the progno- sis of ACC. The control of liver metastases prolongs survival. TACE and bland TAE are reported to be very effective treat- ments for liver malignancy. However, evidence of the survival benefits of TACE and bland TAE for ACC liver metastases re- mains very limited.
Theoretically, bland TAE induces local ischemia by stop- ping arterial blood flow to ACC, leading to tumor cell death. Therefore, bland TAE is more effective in hypervascular tu- mors than in hypovascular tumors. ACC liver metastases have very high vascular density at 573.2 ± 185.2/mm2 [17]. This den- sity is about twice that of HCC (297 ± 88/mm2) [18]. Therefore, bland TAE for ACC liver metastases can be expected to have the same favorable therapeutic effect as that for HCC [14]. In the present case, CT also showed the hypervascularity of the liver metastases. Bland TAE was very effective as suggested, resulting in the complete response of many nodules.
Some reports have shown the effectiveness of TAE and TACE for liver metastasis. Tanaka et al. reported that repeated bland TAE at 100 um microsphere was very effective against chemoresistant liver metastases of colorectal or gastric can- cer [19]. Shimohira et al. showed that bland TAE mainly at 100-300 um microspheres was effective for hypervascular liver metastases refractory to standard treatment. They reported overall response and disease control rates of 52% and 72%, re- spectively. However, the complete response rate was only 8%
A
B
C
D
Z 1.18 C 2047. 1 4095.
Resection of the left adrenocortical carcinoma
Posterior segmentectomy plus S5 partial hepatectomy
S4 partial hepatectomy
2 lesions of 2 cm or less remain.
Two cycles of EDP-m therapy started.
Multiple new liver metastases observed.
2 of 3 lesions got CR.
4 of 5 lesions got CR.
2 of 4 lesions got CR.
X X+1
X+3
X+3
X+4
X+4
X+5
X+6
X+8
Multiple metastases of the liver and lung were found. Mitotane therapy started.
Bland TAE12
Bland TAE 3
Bland TAE 456
Mitotane therapy continues. Lung metastases are slowly growing but well controlled.
[11]. With reference to this report, we used 100-300 um micro- spheres as the embolic material.
Reports of TACE and bland TAE for ACC liver metastases are even more limited. Wong et al. reported a complete re- sponse of liver metastases in a patient who underwent con- ventional TACE with doxorubicin, mitomycin, and iodized oil after EDP-M chemotherapy [16]. Their limitation was that the lesions were evaluated only by positron emission tomography. Soga et al. described a complete response of liver metastases in 2 patients who underwent bland TAE after EDP-M [14]. Owen et al. reported that patients receiving additional local thera- pies such as TACE or selective internal radiation therapy had a significantly longer survival time than patients who did not [20]. These previous reports are expected to further improve the treatment outcomes of TACE and bland TAE. Cazejust et al. reported the analysis of a large number of patients (n = 29) with ACC liver metastases who underwent conventional TACE with cisplatin and iodized oil. In their study, the response rate was only 21%. There are several possible reasons for this poor result. First, conventional TACE with iodized oil may not be ef- fective for ACC liver metastases. Second, CT analysis was not yet mature, and super selective embolization with feeder de- tection was not possible. In the present case, ultra selective bland TAE as a selective embolization treatment supported by the latest CT analysis techniques during arteriography could minimize TAE-induced liver damage and made it possible to perform multiple treatments which prolonged survival. Addi- tionally, the surgical excision of the tumors refractory to bland TAE also produced a favorable outcome. Based on the present case, we conclude that bland TAE can be effective for ACC liver metastases, and it should be considered as a selective em- bolization treatment for ACC similarly to HCC.
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