Right Atrial Extension of Adrenocortical Carcinoma Surgical Management Using Hypothermia and Cardiopulmonary Bypass
POLLY S. Y. CHEUNG, MB, BS, FRCS, AND NORMAN W. THOMPSON, MD
A patient with right adrenocortical carcinoma extending into the inferior vena cava and right atrium is presented. Tumor extension was demonstrated by magnetic resonance imaging (MRI) preoperatively. Successful resection of the adrenal tumor and its intravascular extension was achieved with the help of cardiopulmonary bypass and hypothermia. The patient was maintained on mitotane (o,p’-DDD), and was well for 12 months after surgery. It was concluded that intravascular extension of adrenocortical carcinoma is not a contraindication to radical surgery.
Cancer 64:812-815, 1989.
A DRENOCORTICAL CARCINOMAS generally have poor prognoses because of their high degree of malig- nancy, the late stage of the disease at diagnosis, and the lack of satisfactory adjuvant therapy. Recent studies, however, suggest that aggressive surgical therapy com- bined with adjuvant mitotane therapy may prolong sur- vival even for patients with advanced disease.1 The pres- ence of intravascular extension in an adrenocortical tumor may prevent the surgeon from proceeding with a radical resection, because of which the patient is deprived of a chance for longer survival.2 Here we report on a patient with virilizing right adrenocortical carcinoma extending into the right atrium who underwent successful resection employing hypothermia and cardiopulmonary bypass.
Case Report
A 22-year-old woman was admitted to the University of Michigan Medical Center, Ann Arbor because of a 5-month history of hirsutism, increased acne, increased libido, and amen- orrhea. Twenty-four hour urinary 17-hydroxycorticosteroids were 11.2 mg (normal, 5-10 mg/24 hr) and 24-hour urinary 17- ketosteroids were 45.2 mg (normal, 4-14 mg/24 hr). Urinary free cortisol was 31 ug/day (normal 50-125 µg/day). Plasma cortisol was 6.1 ug/dl in AM and 4.5 µg/dl in PM (normal, 10- 25 ug/dl in AM; 3-16 µg/dl in PM). Plasma testosterone was 2.73 ng/ml (normal, 0.24-0.66 ng/ml), and dehydroepiandros- tenedione sulphate (DHEA-S) was 8560 ng/ml (normal, 820- 3380 ng/ml). Plasma estradiol, FSH, and LH were normal. Plasma prolactin was 26 ng/ml (normal, 2-22 ng/ml). Overnight
dexamethasone test showed normal suppression of plasma cor- tisol. These biochemical studies confirmed the presence of vi- rilizing syndrome with increased testosterone but no excess cor- tisol production.
Abdominal ultrasonography showed a large right suprarenal mass with clear interface with the kidney. Computerized axial tomography scanning demonstrated a right adrenal mass with partial calcification clearly demarcated from the liver. MRI showed a tumor thrombus that extended from the adrenal vein into the inferior vena cava and continued into the right atrium (Figs. 1A and 1B). There was no demonstrable liver, peritoneal, or lymph node metastasis. NP-59 scintigraphy showed normal uptake in the left adrenal but nonvisualization of the right adrenal mass (Fig. 2). This supports the diagnosis of a malignant right adrenal tumor with no suppression of normal ACTH production in the body. Angiography and venography were not performed because the patient was sensitive to iodinated dye.
The patient underwent an operation with the diagnosis of malignant virilizing adrenal tumor. No steroid cover was used because the patient had a normally functioning contralateral adrenal gland and did not have Cushing’s syndrome. After an extended right subcostal incision, the abdomen was explored, confirming the absence of a liver, peritoneal, or lymph node metastasis. The tumor measured about 14 cm in diameter, dis- placing the right kidney downwards and laterally, and was sep- arated from the liver and the right kidney by connective tissue planes (Fig. 3A). The tumor was mobilized by sharp and blunt dissection until it was only attached by the right adrenal vein to the inferior vena cava. The right adrenal vein was dilated to 3 cm in diameter and filled with the tumor. At this point, the heart was approached through a median sternotomy. The patient was put on cardiopulmonary bypass, and hypothermia was obtained by cooling the body to 14℃. Total circulatory arrest was insti- tuted by turning off the pump. The inferior vena cava was opened at the level of the right adrenal vein and part of its wall was trimmed and removed en bloc with the tumor mass. The intra- vascular tumor thrombus was dissected from its attachments to the caval wall (Fig. 3B). The part of the tumor thrombus pro-
From the Division of Endocrine Surgery, University of Michigan Medical Center, Ann Arbor, Michigan.
Address for reprints: Polly S. Y. Cheung, MB, BS, FRCS, Department of Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong. Accepted for publication February 14, 1989.
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truding into the right atrium was pushed down by the cardiac surgeon without resorting to an open atriotomy. All the intra- vascular tumor was removed from the inferior vena cavotomy in one piece (Fig. 3C). The 6 cm defect in the inferior vena cava was closed with 5-0 cardiovascular sutures. Cardiopulmonary bypass was reinstituted and the patient was gradually rewarmed. The patient recovered from the operation uneventfully.
Postoperatively, the patient developed intraabdominal bleed- ing requiring reexploration and hemostasis. There was no neu- rologic deficit. In the postoperative period, she developed epi- sodes of hypotension suspected to be due to adrenal insufficiency and was put on cortisone of 30 mg/day. Mitotane was started and maintained at 3.5 gm/day, a dose that she tolerated well. Decrease in hair growth and return of menstruation were evident 3 weeks after the operation. Serum DHEA fell to 105.4 ng/ml (normal 820-3380 ng/dl) 2 months after the operation. Histo- logic study confirmed the diagnosis of adrenocortical carcinoma. The patient remained well and free of disease for 1 year until she committed suicide for emotional reasons.
Discussion
Adrenocortical carcinomas are highly malignant tu- mors. Approximately 50% to 70% have locally advanced or metastatic disease at the time of presentation.3-6 Intra- caval extension is a known feature of adrenocortical car- cinoma and has been described in several reports.2,7-9 Its presence is potentially hazardous because it can cause caval obstruction, extension of the tumor thrombus into the right atrium causing atrial occlusion, and tumor em- bolization. However, it often remains silent and is diag- nosed only at the time of surgery. In this situation, a small thrombus can be extracted through a simple cavotomy. More commonly, surgeons, without knowing the extent of caval involvement, will consider this as locally advanced disease and resort only to a palliative resection of the pri- mary. Therefore, a preoperative diagnosis of caval in- volvement in suspected adrenal malignancy is essential for planning the extent of surgery.
Approximately half of the adrenocortical carcinomas are nonfunctioning. The tumor, therefore, often becomes large before it is diagnosed. An adrenal tumor of greater than 5 cm in diameter raises the suspicion of malignancy. Bilateral nonvisualization of adrenals in an NP-59 scin- tiscan also supports the diagnosis of adrenocortical car- cinoma because the malignant adrenal tumor tissue is inefficient in producing hormones. Also, uptake of NP- 59 per gram of tumor tissue is too low to allow for visu- alization, although adequate cortisol is produced to sup- press pituitary ACTH release, thereby suppressing the up- take of NP-59 in the contralateral gland.10 The 14 cm size tumor in our patient raised the question of malignancy
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despite the visualization of the contralateral adrenal gland in the NP-59 scan. This is the exception rather than the rule.
In the case of an adrenal tumor that is suspected of being malignant, inferior vena cavography has been rec- ommended as a routine procedure to diagnose caval in- volvement.8 However, it is often difficult to differentiate extrinsic caval compression from intracaval extension of the tumor. In addition to its being an invasive and, there- fore, less desirable study, venography cannot be performed in patients with known sensitivity to iodinated dye. This was the case with our patient. Computed tomography and MRI are noninvasive alternative procedures. Careful in- terpretation of the status of the inferior vena cava at the region of the tumor can often guide further scanning into the thorax. In our patient, MRI demonstrated very clearly the continuous extension of the tumor thrombus into the right atrium.
The most effective therapy in treating adrenocortical carcinoma is surgical extirpation of the tumor.11 The re- sults of radiotherapy and various chemotherapy combi- nations have been poor. Mitotane (o,p’-DDD) was shown in some reports to be useful as an adjunctive therapy that can prolong survival in patients with adrenocortical car- cinoma.1.12 Also, patients suffering from the debilitating symptoms of functioning carcinomas often benefit from a surgical debulking operation despite the presence of metastasis. Attempts at aggressive surgical therapy, there- fore, are justified, and intracaval extension of the tumor should not be a contraindication to radical surgery. The first patient diagnosed preoperatively with adrenocortical carcinoma with right atrial extension died from right atrial occlusion by tumor thrombus soon after surgery because only palliative resection of the primary tumor was per- formed.13 When intracaval involvement by the tumor is known preoperatively, surgery can be planned carefully, with cardiopulmonary bypass as a standby measure. Suc- cessful removal of the tumor has been reported in Wilm’s tumor,14 renal cell carcinoma,15 recurrent pheochromo- cytoma,16 and thyroid carcinoma.17 The case described in this report is the first adrenocortical carcinoma with right atrial extension successfully removed with the aid of hypothermia and cardiopulmonary bypass. The pa- tient’s postoperative course has shown that such aggressive surgery is justified.
We conclude that aggressive removal of intraatrial tu- mor extension in adrenocortical carcinomas, with the help of cardiopulmonary bypass, is a safe procedure that is justified from the point of complete surgical resection, allowing for a more effective adjuvant mitotane therapy and preventing vascular complications.
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