CASE REPORT
Extended Survival in a Patient With Recurrent and Metastatic Adrenal Cortical Carcinoma by Aggressive Transarterial Embolization-a Case Report
SHAU-HSUAN LI, MD,1 CHENG-HUA HUANG, MD,1* SHEUNG-FAT KO, MD,2 FONG-FU CHOU, MD,3 AND SHUN-CHEN HUANG, MD4
1 Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
2Department of Radiology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
3 Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
4Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
The prognosis of inoperable recurrent or metastatic adrenal cortical carcinoma is poor due to lack of effective treatment modalities. We report a case of recurrent and meta- static adrenal cortical carcinoma in which prolonged survival of 58 months was achieved with aggressive three sequential transarterial embolization. It is probably the first reported case with the longest survival by transarterial embolization in the litera- ture to date. A 60-year-old man received operation for left adrenal cortical carcinoma. Liver metastases, tumor bed recurrence, and spleen metastasis were noted during follow-up. Three sequential transarterial embolization for metastatic liver tumors, tumor bed recurrence, and metastatic spleen tumor were performed and resulted in relief of symptoms and prolonged survival of 58 months after recurrence verified. Aggressive transarterial embolization seems to be a safe and effective procedure for symptoms relief, and may prolong survival in the management of inoperable adrenal cortical carcinoma. It can be considered in any patient with inoperable adrenal cortical carcinoma if not contraindicated.
J. Surg. Oncol. 2005;90:101-105. @ 2005 Wiley-Liss, Inc.
KEY WORDS: transarterial embolization; adrenal cortical carcinoma; recur- rent; metastatic
INTRODUCTION
Adrenal cortical carcinoma is a rare and highly malig- nant neoplasm with a worldwide incidence of approxi- mately 0.5-2 cases per one million population per year, accounting for 0.2% of all cancer-related deaths [1,2]. The tumors may be functional or non-functional, depend- ing on whether they produce cortisol, aldosterone, or sex hormones. The non-functional tumors are more frequent, reach a conspicuous size to cause mass effect or pain without clinical signs or symptoms of endocrine dys- function and often are discovered at an advanced stage [3]. The survival rate is low both for functional and non- functional adrenal cortical carcinoma, the latter usually being considered to have a poor prognosis due to the
delay in diagnosis [4-6]. The mainstay of therapy is still the radical surgical resection of the tumor. Even after complete and radical surgical excision, locoregional re- lapse or distant metastases are common. The treatment modalities, such as mitotane or other chemotherapy for inoperable recurrent or metastatic adrenal cortical carci- noma, have limited effect, and the outcome is very poor.
*Correspondence to: Cheng-Hua Huang, MD, Department of Internal Medicine, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niaosung Hsiang, Kaohsiung Hsien, Taiwan, R.O.C. Fax: 886-7-7322402.
E-mail: lee.a0928@msa.hinet.net
Received 8 October 2004; Accepted 16 March 2005
DOI 10.1002/jso.20247
Published online in Wiley InterScience (www.interscience.wiley.com).
@ 2005 Wiley-Liss, Inc.
There seems to be no report of prolonged survival in patients with inoperable recurrent or metastatic adrenal cortical carcinoma by application of transarterial embo- lization. We report a patient of recurrent and metastatic non-functional adrenal cortical carcinoma, who received three sequential transarterial embolization for metastatic liver tumors, tumor bed recurrence, and metastatic spleen tumor, got a prolonged survival of 58 months after recurrence verified.
CASE REPORT
The patient was a 60-year-old man who presented with clinical manifestations of abdominal pain and fullness in October 1996. There was no weight gain, centripetal obesity, muscle wasting, hypertension, acne, hirsutism, and gynecomastia. Abdominal computed tomography revealed a 9 cm mass in the retroperitoneal area. Total excision of retroperitoneal tumor with a complete margin-negative resection was performed in December 1996, and there was no breach of the capsule found by surgeon. The histopathological examination revealed a adrenal cortical carcinoma (Fig. 1) formed by large pleomorphic cells with high mitotic rate (mitotic rate is 23 per 50 high power fields), atypical mitoses, extensive necrosis, and hemorrhage. The maximum diameter of tumor was 10 cm. No tumor cell invasion into the sur- rounding tissue and no metastasis could be seen at the time of the diagnosis (T2N0M0 according to stage II, using the staging system by MacFarlane [7]). From the clinical point of view, the non-functional adrenal cortical carcinoma is most likely.
After 20 months of disease-free survival, recurrence with multiple liver metastases and 3 x 3 cm abdominal wall mass were found during follow-up. The patient complained of abdominal fullness and pain, but he hesitated about mitotane and other chemotherapy.
In October 1998, transarterial hepatic embolization in right lobe of liver (Fig. 2) was performed with 2 ml 2% xylocaine, 6 ml 95% alcohol, 12 ml lipiodol, and gelfoam powder uneventfully. Besides, abdominal wall mass was also completely resected in October 1998, and histo- pathological examination showed a metastasis of the adrenal cortical carcinoma. The abdominal fullness and pain were relieved later. Three months later, follow-up computerized tomography of the abdomen disclosed shrunken liver masses with well lipiodol stasis.
In June 2000, 7 cm tumor bed recurrence and 6 cm spleen metastasis were noted by abdominal computed tomography. The abdominal fullness and pain progressed gradually. In July 2001, transarterial embolization of tumor bed recurrence was done. Angiography showed a large tumor in lateral aspect superior part of the left kidney with multiple supplies from upper left renal interlobar and interlobular arteries. Supply from left superior adrenal artery is also noted. Transarterial embolization of the tumor bed recurrence (Fig. 3) was performed after superselective catherization of the left renal interlobar arteries with 3 ml 95% alcohol and 9 ml lipiodol as well as gelfoam powder. Additionally, in October 2001, transarterial embolization of the metastatic spleen tumor (Fig. 4) was done after selective catheriza- tion of the slenic artery with 6 ml 95% alcohol and 18 ml lipiodol as well as gelfoam powder. After these two intervention, the abdominal fullness and pain improved. In December 2001, follow-up computerized tomography of the abdomen revealed regressive change of tumor bed recurrence with 40% lipiodol stasis and metastatic spleen tumor with 85% lipiodol stasis. Finally, this patient died of pneumonia in May 2003. He died 58 months after recurrence verified.
DISCUSSION
The only potentially curative treatment for adrenal cortical carcinoma is the complete surgical resection of the tumor. After complete and curative resection, the 5- year survival is about 38-62% whereas untreated patients have a very poor prognosis with a mean survival of only 3-6 months. Patients with incomplete primary resection have a mean survival of less than 12 months with a 5-year survival rate of 0-9% [4,8-17]. This demonstrates the impact of a complete margin-negative surgical resection on the survival.
Even for patients who undergo complete resection, recurrent and metastatic disease are extremely common.
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The chemotherapeutic agent most often used to treat inoperable recurrent, or metastatic adrenal cortical carci- noma is mitotane, but the effect is limited [16,18,19]. The response rate is about 14-29% without survival benefit [16,18,19]. Venkatesh et al. [18] reported an objective partial response rate of 29% in 72 patients treated with mitotane, but the 2-year survival was only 13%. Besides, there is significant toxicity associated with mitotane therapy [20]. Almost all patients experience gastrointest- inal symptoms including nausea and anorexia. Neuro- muscular toxicity including depression, somnolence, and dizziness has been noted in 40-60% of patients. Many patients are unable to perform normal work or leisure activities due to side effects. Adrenal insufficiency is almost universal in patients taking mitotane secondary to its toxicity against normal adrenal tissue.
The only effective treatment for recurrent adrenal cortical carcinoma is reoperation [12,14,16,17,21,22]. Resection of recurrent and metastatic disease when com- plete is associated with long-term survival and provides excellent palliation for pain and endocrine symptoms. Richard D. Schulick and Murray F. Brennan [14] reported in Memorial Sloan-Kettering Cancer Center that 47 patients with relapse after primary resection underwent a second resection for local or distant recurrence. Thirty two patients undergoing a complete resection had a median survival of 74 months after second resection (5-
year survival, 57%). Fifteen patients undergoing an incomplete resection had a median survival of 16 months (5-year survival, 0%) and all died within 36 months after second resection. Bellantone et al. [17] presented that 23% of the reoperated patients were alive at 3 years after recurrence, whereas there were no survivors at 1 year after recurrence in the nonreoperated group. Our patient did not receive complete second operation and got a prolonged survival of 58 months after recurrence by three sequential transarterial embolization for multiple liver metastases, tumor bed recurrence, and metastatic spleen tumor. The survival of our patient after recurrence is better than any patient without complete second resection in Memorial Sloan-Kettering Cancer Center and Bellan- tone et al. series. It demonstrated that transarterial embolization can be one of the therapeutic modalities and improved survival in inoperable, recurrent, or metastatic adrenal cortical carcinoma. Reviewing pre- vious literature, there were only two studies about transarterial embolization for adrenal cortical carcinoma [23,24]. O’Keeffe et al. [23] reported adrenal arterial embolization in four patients with inoperable adrenal cortical carcinoma. They found adrenal arterial emboli- zation may play an effective role without serious side effect in palliation of pain and reduction of hormone production in inoperable adrenal lesions. However, these four patients died 20 months, 12 months, 2 months, and
2 months after initial embolization. Koh et al. [24] presented a case of metastatic adrenal cortical carcinoma in which partial remission was achieved with transarterial embolization for multiple liver metastases. But this patient died 6 months after recurrence. Our patient sur- vived longer than those in the above two studies. Aggressive three sequential transarterial embolization may be the cause of difference in survival. To our know- ledge, our case report seems to have the longest survival after recurrence achieved by transarterial embolization in inoperable recurrent and metastatic adrenal cortical carcinoma in the world.
Except transarterial embolization, the other form of cytoreduction therapy such as radiofrequency ablation has been reported before. Wood et al. [25] reported the percutaneous, image-guided radiofrequency ablation in 8 patients with 15 adrenal cortical carcinoma recurrences or metastases. They found this procedure is efficacious in the short-term local control of small adrenal tumors. In the future, we need more clinical studies to evaluate the survival impact of transarterial embolization or radio- frequency ablation in patients with inoperable adrenal cortical carcinoma.
We concluded that aggressive transarterial emboliza- tion for inoperable adrenal cortical carcinoma is a safe and effective procedure for symptom relief, and may prolong survival. It should be considered in any patient with inoperable recurrent or metastatic adrenal cortical carcinoma if not contraindicated.
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