2388676

11. Saito Y, Nakao K, Arai H, et al. Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart. J Clin Invest 1989; 83:298-305.

12. Yasue H, Obata K, Okumura K, et al. Increased secretion of atrial natriuret- ic polypeptide from the left ventricle in patients with dilated cardiomyopa- thy. J Clin Invest 1989; 83:46-51.

13. Criteria Committee of the New York Heart Association. Diseases of the heart and blood vessels, nomenclature and criteria for diagnosis. 6th ed. Boston: Little, Brown, 1964.

14. Chang MS, Lowe DG, Lewis M, Hellmiss R, Chen E, Goeddel DV. Differ- ential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases. Nature 1989; 341:68-72.

MITOTANE THERAPY OF ADRENOCORTICAL CARCINOMA

To the Editor: The paper on adrenocortical carcinoma by Luton et al. (April 26 issue)’ included a description of the results of mitotane therapy (Roussel-UCLAF) in 59 patients. The drug was given in capsules containing 0.5 g of micronized mitotane mixed with cellu- lose acetylphthalate. The side effects of mitotane were minimal, contrary to what others have reported.2 Tumor response, which could be evaluated in 37 patients, was low: 8 patients (22 percent) had tumor regression (ranging from 10 to 80 percent) for 5 to 25 months. The other patients had progressive (73 percent) or stable (5 percent) disease. Mitotane therapy did not significantly prolong survival. However, our group (van Slooten et al.3) found that sur- vival was significantly prolonged in patients with serum mitotane levels of more than 14 mg per liter. The response rate to mitotane ranged from 20 to 60 percent in other studies.2,4 Considering the relatively low frequency of side effects in the patients treated by Luton et al., the low response rate to mitotane therapy could be explained by low serum mitotane levels. Moolenaar et al.5 measured serum mitotane levels after the oral administration of mitotane in various vehicles. They found that micronized mitotane resulted in significantly lower serum levels than mitotane given in any other vehicle tested. Thus, the results of treating adrenocortical carcino- ma with micronized mitotane might be influenced by impaired re- sorption of the drug. We wonder whether mitotane levels were measured by Luton et al., and if measured, how the levels achieved relate to tumor response and patient survival.

HARM R. HAAK, M.D. ARNOUD P. VAN SETERS, M.D. ABRAHAM J. MOOLENAAR, PH.D. University Hospital Leiden

2300 RC Leiden, the Netherlands

1. Luton J-P, Cerdas S, Billaud L, et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 1990; 322:1195-201.

2. Gutierrez ML, Crooke ST. Mitotane (o,p’-DDD). Cancer Treat Rev 1980; 7:49-55.

3. van Slooten H, Moolenaar AJ, van Seters AP, Smeenk D. The treatment of adrenocortical carcinoma with o,p’-DDD: prognostic implications of serum level monitoring. Eur J Cancer Clin Oncol 1984; 20:47-53.

4. Samaan NA, Hickey RC. Adrenal cortical carcinoma. Semin Oncol 1987; 14:292-6.

5. Moolenaar AJ, van Slooten H, van Seters AP, Smeenk D. Blood levels of o,p’-DDD following administration in various vehicles after a single dose and during long-term treatment. Cancer Chemother Pharmacol 1981; 7:51-4.

The above letter was referred to the authors of the article in question, who offer the following reply:

To the Editor: Haak et al. raise an important question that we addressed in our discussion. After a single dose of mitotane, serum levels are lower when the drug is given in micronized form than when it is given in other vehicles, such as tablets, milk, chocolate, or emulsion.1 Yet one has to consider the effects of long-term adminis- tration. We have found that in patients given micronized mitotane, maximal mitotane levels were reached only after six to eight weeks of treatment. Thereafter, the steady-state concentration ranged from 9 to 28 mg per liter. We do not have enough data to assess the predictive value of these measurements. Many patients had some side effects, usually mild gastrointestinal or neurologic symptoms, and most had biochemical disturbances indicative of mitotane ac- tion, in addition to adrenal suppression. As a practical matter pa-

tients are given the maximal tolerable dose so that, as van Slooten et al. suggest,2 levels of mitotane will be close to if not higher than 14 mg per liter. Whether this value really distinguishes the patients who will eventually benefit from the treatment in terms of pro- longed survival from those who will not remains to be confirmed: the patients of van Slooten et al.2 who survived longer not only had the highest serum mitotane values but also had tumors in lower stages and better Karnofsky indexes; differences in age, which we found to be a good prognostic indicator, were not mentioned.2

Although mitotane did not have a statistically significant effect in our study, perhaps because of its unavoidably retrospective nature, we think there is sufficient evidence of its benefit in some patients that it should be used as adjuvant therapy after aggressive surgery.

	JEAN-PIERRE LUTON, M.D. SONIA CERDAS, M.D.
	LINE BILLAUD, M.D.
75674 Paris, France	Hôpital Cochin
	GUY THOMAS, M.D.
Paris, France	Hôpital Fernand Widal
BRIGITTE GUILHAUME, M.D., XAVIER BERTAGNA, M.D., MARIE-HÉLÈNE LAUDAT, M.D., ALBERT LOUVEL, M.D.,
	AND YVES CHAPUIS, M.D.
75674 Paris, France	Hôpital Cochin
Paris, France	PHILIPPE BLONDEAU, M.D. Hôpital Broussais
	ANDRÉ BONNIN, M.D. HENRI BRICAIRE, M.D.
75674 Paris, France	Hôpital Cochin

1. Moolenaar AJ, van Slooten H, van Seters AP, Smeenk D. Blood levels of o,p’-DDD following administration in various vehicles after a single dose and during long-term treatment. Cancer Chemother Pharmacol 1981; 7:51-4.

2. van Slooten H, Moolenaar AJ, van Seters AP, Smeenk D. The treatment of adrenocortical carcinoma with o,p’-DDD: prognostic implications of serum level monitoring. Eur J Cancer Clin Oncol 1984; 20:47-53.

MEDIASTINAL EMPHYSEMA AFTER A SAX ORGY

To the Editor: We recently cared for a 24-year-old man admitted to the emergency room with symptoms of substernal chest discomfort, breathlessness, difficulty swallowing, and change in speech. The patient stated that he had been well until the evening before admis- sion, when he first noticed these symptoms after three hours of vigorous saxophone playing. His medical history was otherwise un- remarkable. The patient is a nonsmoker and has no history of respi- ratory disorders. Physical examination was remarkable for crepi- tance in the neck and a mediastinal crunch that varied with the cardiac cycle. A chest film was remarkable for air in the neck and mediastinum, as well as in the pericardium. No pneumothorax was present. Other laboratory studies were also normal. The patient was admitted to the hospital for observation and oxygen therapy. His symptoms improved over two days, and he was discharged with no further signs or symptoms of pneumomediastinum. A subsequent chest film was also normal.

The hazard of hypersensitivity pneumonitis in a saxophone play- er has previously been reported.1 However, we have been unable to find evidence of previously reported barotrauma due to saxophone playing. A review of the medical problems of musicians2 makes no mention of the potential for barotrauma with wind instruments. However, it has been noted that high intrathoracic pressure from oboe or trumpet playing may impair venous return.3 Reviews on barotrauma and mediastinal emphysema have not mentioned wind instruments,4,5 although other unusual causes of barotrauma have been reported.6-8

We wish to bring to the attention of other physicians the potential risk apparently associated with some wind instruments. In the ab- sence of clear guidelines in the medical literature, we had few specif- ic recommendations for our patient other than our instruction to “practice safe sax” in the future.

RICHARD W. SNYDER, M.D. HENRY S. MISHEL, M.D. G. CHRIS CHRISTENSEN, III, D.O. Abington Pulmonary Associates, Ltd.

Abington, PA 19001